Sulfonamide derivatives

ABSTRACT

Sulfonamide derivatives of the general formula (I): ##STR1## wherein preferably R 1  represents a lower alkoxy group, R 2 , R 3 , R 4 , R 5 , R 6  and R 7  are as defined in the specification, A and B may be the same or different from each other and each represents ═N-- or ═CH--, E represents an aromatic 6-membered cyclic group, which may have 1 or 2 nitrogen atoms in the ring, and may be substituted with 1 to 3 substituents which may be the same or different from one another with the proviso that a combination of R 1  which is a hydrogen atom, lower alkyl group, nitro group or amino group which may be protected, R 2  and R 3  which are each a hydrogen atom, A and B which are each ═CH-- and E which is a phenyl group which may be substituted with 1 to 3 substituents G which may be the same or different from one another is excluded, or pharmacologically acceptance salts of them.

FIELD OF INDUSTRIAL APPLICATION

The present invention relates to new sulfonamide derivatives, processesfor producing them and a medicinal composition containing the same asthe active ingredient.

Chemotherapeutic agents for cancers used heretofore include varioussubstances, for example, alkylating agents such as cyclophosphamide,antimetabolites such as methotrexate and fluorouracil, antibiotics suchas adriamycin, mitomycin and bleomycin, those derived from plants suchas vincristine and etoposide, and metal complexes such as cisplatin.

4-Aminobenzenesulfonamide derivatives (see Japanese Patent PublicationNo. 3093/1968), 2-sulfonylamide/quinoxaline derivatives (see JapanesePatent Laid-Open No. 426/1987) and m-AMSA derivatives (see J. Med.Chem., 18, 1110 (1975)) were reported as active antineoplastic compoundshaving a sulfonamide group.

Most of them have only a low effectiveness on human tumors, particularlysolid tumors having a low growth rate, such as lung cancer or coloncancer, and exhibit serious adverse reactions. Under thesecircumstances, the development of a new medicine having only a lowtoxicity and an excellent antitumor activity is demanded.

An object of the present invention is to provide new sulfonamidederivatives having an excellent antitumor activity and only a lowtoxicity. Another object of the present invention is to provide aprocess for producing these compounds and a medicinal compositioncontaining them as the active ingredient.

SUMMARY OF THE INVENTION

After intensive investigations made for the purpose of finding anantitumor compound having only a low toxicity as described above, theinventors have found that new sulfonamide derivatives, which will bedescribed below, have an excellent antitumor activity and only a lowtoxicity. The present invention has been completed on the basis of thisfinding.

Thus the present invention relates to sulfonamide derivatives of thegeneral formula (I) or pharmacologically acceptable salts of them:##STR2## wherein: R¹ represents a hydrogen atom, halogen atom, loweralkyl group, lower alkoxy group, hydroxyl group, nitro group, phenoxygroup, cyano group, acetyl group or amino group, which may be protected,

R² and R³ may be the same or different from each other and eachrepresent a hydrogen atom, halogen atom, lower alkyl group or loweralkoxy group,

R⁴ and R⁷ may be the same or different from each other and eachrepresent a hydrogen atom or lower alkyl group,

R⁵ and R⁶ may be the same or different from each other and eachrepresent a hydrogen atom, halogen atom, lower alkoxyl group or aminogroup which may be substituted,

A represents a group of the formula: ═N-- or ═CH--,

B represents a group of the formula: ##STR3## in which R¹⁰ represents ahydrogen atom or lower alkyl group,

E represents a group of the formula: ##STR4## in which Q represents anoxygen atom or sulfur atom and R¹¹ represents a hydrogen atom, loweralkyl group, amino group which may be substituted with a lower alkylgroup, lower alkoxy group, 2-thienyl group, 2-furyl group or group ofthe formula: ##STR5## being a group of the formula: ═N-- or ═CH--,

and R¹² and R¹³ being the same or different from each other and eachbeing a hydrogen atom, halogen atom, nitro group, hydroxyl group, whichmay be protected, or lower alkyl group; or an aromatic 6-membered cyclicgroup which may be substituted with 1 to 3 substituents G, which may bethe same or different from one another, and which cyclic group may have1 or 2 nitrogen atoms in the ring, G being a halogen atom, lower alkylgroup, lower alkoxy group, hydroxyl group which may be protected,carboxyl group which may be esterified or amidated, lower alkylthiogroup or phenoxy group, with the proviso that the following combinationsare excluded:

(1) a combination of R¹ which is a hydrogen atom, lower alkyl group,nitro group or amino group, which may be protected, R² and R³ are each ahydrogen atom, A and B are each ═CH-- and E is a phenyl group which maybe substituted with 1 to 3 substituents G, which may be the same ordifferent from one another, and

(2) a combination of R¹, R² and R³, which may be the same or differentfrom one another and which are each a hydrogen atom, lower alkyl group,nitro group or halogen atom, A and B are each ═CH--,

and E is a group of the formula: ##STR6## in which R¹¹ is a lower alkylgroup, amino group, which may be substituted with a lower alkyl group,or a group of the formula: ##STR7##

R¹² and R¹³ being each as defined above.

The detailed description will now be made of the present invention.

The lower alkyl groups in the definition of R¹, R², R³, R⁷, R¹⁰, R¹¹,R¹², R¹³ and the substituent G which may be substituted in thedefinition of E of the above general formula (I) include straight-chainand branched alkyl groups having 1 to 6 carbon atoms, such as methyl,ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl,n-pentyl (amyl), isopentyl, neopentyl, tert-pentyl, 1-methylbutyl,2-methylbutyl, 1,2-dimethylpropyl, n-hexyl, isohexyl, 1-methylpentyl,2-methylpentyl, 3-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl,2,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl,3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl,1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropylgroups. Among them, methyl, ethyl, propyl and isopropyl groups arepreferred, with methyl and ethyl groups being most preferred.

The lower alkoxy groups in the definition of R¹, R², R³, R⁵, R⁶, R¹¹ andthe substituent G which may be substituted in the definition of E arethose derived from the above-described lower alkyl groups, such asmethoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy and t-butoxygroups. Among them, the most desirable are methoxy and ethoxy groups.The halogen atoms include fluorine, chlorine and bromine atoms.

The substituted amino groups in the definition of R⁵ and R⁶ includeamino groups substituted with a lower alkyl group, such as methylamino,ethylamino and dimethylamino groups, and amino groups substituted with aphenyl group.

The hydroxyl groups which may be protected of the substituent G, whichmay be substituted in the definition of E, include hydroxyl,methoxymethyloxy, tetrahydropyranyloxy, benzyloxy, phosphoric ester,sulfuric ester, sulfonic ester, such as an ester ofp-methoxybenzenesulfonic acid or methanesulfonic acid, amino acid ester,such as an ester of glycine, alanine, leucine, tyrosine, aspartic acid,glutamic acid, lysine, arginine, proline, sarcosine, β-alanine orγ-aminobutyric acid, glycoside, such as glucoside and glucuronide,carbamoyloxy which may be substituted with a lower alkyl, such ascarbamoyloxy, methylcarbamoyloxy and dimethylcarbamoyloxy, lower acyloxyhaving 1 to 5 carbon atoms, such as formyloxy, acetoxy, propionyloxy andpivaloyloxy and benzoyloxy.

The aromatic ring of the benzoyloxy group may be, if desired,substituted with a lower alkyl group such as a methyl, ethyl, n-propylor isopropyl group, a lower alkoxy group such as a methoxy, ethoxy,n-propoxy or isopropoxy group, a halogen atom such as a fluorine,chlorine or bromine atom or an amino group which may be substituted witha lower alkyl group.

The amino groups which may be protected in the definition of R¹ includeunsubstituted amino group, lower acylamino groups having 1 to 4 carbonatoms, such as formylamino, acetamino and propionylamino groups, andbenzyloxycarbonylamino group.

The carboxyl groups which may be esterified or amidated in thedefinition of the substituent G which may be substituted in thedefinition of E include carboxyl group, lower alkoxycarbonyl groupshaving 2 to 5 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl andisopropyloxycarbonyl groups, unsubstituted aminocarbonyl group, andaminocarbonyl groups substituted with an alkyl group having 1 to 4carbon atoms, such as methylaminocarbonyl, ethylaminocarbonyl anddimethylaminocarbonyl groups.

The sulfonamide derivatives represented by the above general formula (I)may form a salt with an acid or base. The salts of the compounds (I) arealso included in the present invention. Examples of the salts of themwith an acid include inorganic acid salts such as hydrochloride,hydrobromide and sulfate as well as organic acid salts such as acetate,lactate, succinate, fumarate, maleate, citrate, benzoate,methanesulfonate and p-toluenesulfonate. Examples of the salts of themwith a base include inorganic salts such as sodium, potassium andcalcium salts and salts with organic bases such as triethylamine,arginine and lysine.

As a matter of course, hydrates of these compounds and optical isomers,if present, are also included in the present invention. The compounds ofthe present invention exhibit a potent antineoplastic activity.Compounds which exhibit an antineoplastic activity upon undergoingmetabolism such as oxidation, hydrolysis or conjugation in vivo are alsoincluded in the present invention.

The compounds (I) of the present invention can be produced by variousprocesses. Typical processes among them are as follows:

(1) A sulfonic acid of the general formula (II) or its reactivederivative: ##STR8## wherein R² and R³ are as defined above and R¹ _(a)represents a hydrogen atom, halogen atom, or lower alkyl, lower alkoxy,protected hydroxyl, nitro, phenoxy, cyano, acetyl or protected aminogroup, is reacted with a compound of the general formula (III): ##STR9##wherein R⁴, R⁷, A, B and E are each as defined above, and R⁵ _(a) and R⁶_(a) may be the same or different from each other and each represent ahydrogen or halogen atom, lower alkoxy, or protected or substitutedamino group.

The reactive derivatives of the sulfonic acids (II) include thoseusually used, such as sulfonyl halide, sulfonil anhydride andN-sulfonylimidazolide. Among them, particularly preferred is sulfonylhalide. The reaction proceeds when they are used in stoichiometricallyequimolar amounts. Although the solvents used for the reaction are notparticularly limited, desirable solvents are those in which the startingmaterials are soluble and which do not easily react with the startingmaterials. The solvents are, for example, pyridine, tetrahydrofuran,dioxane, benzene, ether, methylene chloride, dimethylformamide andmixtures of two or more of them. When an acid is liberated as thereaction proceeds, as in the case a sulfonyl halide, the reaction isdesirably conducted in the presence of a suitable acid binder.Therefore, the use of a basic solvent such as pyridine is particularlypreferred. When a neutral solvent is used, a basic substance such as analkali carbonate or an organic tertiary amine may be added. As a matterof course, the solvents usable herein are not limited to those describedabove. The reaction usually proceeds at room temperature and, ifdesired, may be conducted under cooling or heating. The reaction timeusually ranges from 10 min to 20 h. It is suitably determined dependingon the varieties of the starting compounds and reaction temperature.

When the amino, hydroxyl or carboxyl group in the resulting sulfonamidederivative (I) is protected, it can be subjected to an ordinary methodof removing protective groups, such as an acid treatment, alkalitreatment or catalytic reduction, if desired, to obtain a compound (I)having a free hydroxyl, amino or carboxyl group.

(2) A compound of the general formula (IV) ##STR10## wherein R¹ _(a),R², R³, R⁴, R⁵ _(a), R⁶ _(a), R⁷, A and B are each as defined above, andEa represents an aromatic 6-membered cyclic group, which may contain 1or 2 nitrogen atoms in the ring, substituted with 1 to 3 substituents Gawhich may be the same or different from one another, Ga being a halogenatom, lower alkyl group, lower alkoxy group, hydroxyl group, carboxylgroup, which may be esterified or amidated, lower alkylthio group orphenoxy group, with the proviso that at least one Ga on the ring is ahydroxyl group,

is reacted with a compound of the general formula (V):

    X--Y                                                       (V)

wherein X represents a group capable of bonding with the oxygen atom ofthe hydroxyl group and Y represents a removable group,

or with an inorganic acid or organic acid anhydride reactive with thehydroxyl group.

X--Y include reactive derivatives of aromatic and aliphatic sulfonicacids, aromatic and aliphatic carboxylic acids, amino acids which may beprotected, phosphoric acid which may be protected, sulfuric acid whichmay be protected, carbamic acid which may be substituted with a loweralkyl group and saccharides which may be protected. Examples of theminclude p-methoxybenzenesulfonyl chloride, methanesulfonyl chloride,o-chlorobenzoyl chloride, acetyl chloride,N-(t-butoxycarbonylaminoacetyl)imidazole, phosphorus oxychloride,chlorosulfonic acid, N,N-dimethylcarbamoyl chloride and methyl1,2,3,4-tetra-O-acetyl-D-glucuronate. Examples of the anhydrides includeinorganic acid anhydrides, such as diphosphorus pentoxide and sulfurtrioxide, as well as organic acid anhydrides, such as N-carboxyanhydrides (NCA) of α-amino acids and isatoic anhydride.

Although the solvents used in the reaction are not particularly limited,desirable solvents are those in which the starting materials are solubleand which do not easily react with the starting materials. The solventsare, for example, pyridine, tetrahydrofuran, dioxane, benzene, ether,methylene chloride, dimethylformamide and mixtures of two or more ofthem. When a liquid starting compound such as phosphorus oxychloride isused, the reaction can be conducted without using any solvent.

(3) A compound of the general formula (VI): ##STR11## wherein R¹ _(a),R², R³, R⁵ _(a), R⁶ _(a), R⁷, A, B and E are each as defined above,

is reacted with a compound of the general formula:

    R.sup.4.sub.a --L

wherein R⁴ _(a) represents a lower alkyl group and L represents ahalogen atom,

in the presence of a base such as sodium hydride.

(4) A compound of the general formula (VII): ##STR12## wherein R¹ _(a),R², R³, R⁴, R⁵ _(a), R⁶ _(a), A and B are each as defined above,

is reacted with a compound of the general formula (VIII):

    R.sup.11 --Z                                               (VIII)

wherein R¹¹ is as defined above, and Z represents a carboxyl group orits reactive derivative,

or when R¹¹ is a lower alkylamino group, it is reacted with a loweralkyl isocyanate.

The reactive derivatives of the carboxylic acids usable herein are, forexample, acid halides, acid anhydrides, active amide compounds andactive esters.

Examples of the acid halides usable herein are, for example, acidchlorides and acid bromides. The acid anhydrides usable herein are, forexample, mixed monoalkylcarbonic acid anhydrides, mixed acid anhydridescomprising aliphatic carboxylic acids, such as acetic acid, pivalicacid, valeric acid, isovaleric acid and trichloroacetic acid, mixedaromatic carboxylic acids, such as benzoic acid, and symmetric acidanhydrides. The active amide compounds usable herein are, for example,amides of acids with imidazole, pyrazole, 4-substituted imidazole,dimethylpyrazole, triazole, tetrazole and benzothiazole. The activeesters are suitably selected from among methyl esters, methoxymethylesters, cyanomethyl esters, propargyl esters, 4-nitrophenyl esters,2,4-dinitrophenyl esters, trichlorophenyl esters, pentachlorophenylesters, methanesulfonylphenyl esters, phenylazophenyl esters and esterswith 1-hydroxy-1H-2-pyridone, N-hydroxysuccinimide, N-hydroxyphthalimideor 1-hydroxybenzotriazole.

The carboxylic acid (VIII) can be reacted with the amine (VII) in thepresence of a condensing agent such as N,N'-dicyclohexylcarbodiimide(DCC) or N-cyclohexyl-N'-morpholinoethylcarbodiimide.

When R¹¹ is an amino group substituted with a lower alkyl group, theamine (VII) may be reacted with a lower alkyl isocyanate. When R¹¹ is anamino group, the amine (VII) may be reacted with an alkali metal salt ofcyanic acid.

These reactions can be conducted in the presence of a base such as anorganic tertiary amine, e.g. triethylamine, N,N-dimethylaniline orpyridine, alkali carbonate or alkali hydrogencarbonate or an acid, ifnecessary. The reaction proceeds when the reactants are each used in astoichiometrically equimolar amount. Although the solvents used in thereaction are not particularly limited, desirable solvents are those inwhich the starting materials are soluble and which do not easily reactwith the starting materials. The solvents are, for example, pyridine,tetrahydrofuran, dioxane, benzene, ether, methylene chloride,dimethylformamide and mixtures of two or more of them. When a reagentdifficultly soluble in the organic solvent, such as a cyanate, is used,the reaction may be conducted under hydrous conditions. The solventsusable herein are not limited to those described above. The reactiontemperature is not particularly limited so far as the reaction proceeds.It is usually room temperature and, if desired, the reaction may beconducted under cooling or heating. The reaction time usually rangesfrom 5 min to 20 h. It is suitably determined depending on the varietiesof the starting compounds and reaction temperature. When the product hasa protected hydroxyl or amino group, it can be subjected to an ordinarymethod of removing protective groups, such as an acid treatment, alkalitreatment or catalytic reduction to obtain a compound (I) having a freehydroxyl or amino group. When the product has a nitro group, this groupmay be converted into an amino group by reducing it by an ordinarymethod of reducing nitro groups, such as catalytic reduction conductedin the presence of a palladium/carbon catalyst or a method wherein zincpowder and hydrochloric acid are used.

Next the description will be made on the processes for producing thestarting compounds (IX) used in the present invention: ##STR13## whereinR⁵ _(a), R⁶ _(a), R⁷, A, B and E are each as defined above,

or salts of them.

Production process 1 ##STR14## wherein L represents a halogen atom andR⁵ _(a), R⁶ _(a), R⁷, A, B and E are each as defined above.

The compounds of the general formula (XII) can be synthesized by variousprocesses described in publications such as J. Med. Chem., Vol. 21, p.965, J. Org. Chem., Vol. 28, p. 3114, J. Chem. Soc. Perkin I, 1974,1611, 1974, 1970 and 1979, 135, Helv. Chim. Acta, Vol. 61, p. 2452 orprocesses analogous to them. Namely, they can be produced by reacting acompound of the general formula (X) with a compound of the generalformula (XI) in the presence or absence of an organic solvent, such asdimethylformamide, ethanol or dioxane, at room temperature or underheating.

When it is desired to remove a hydrogen halide thus formed, an organicbase such as triethylamine or pyridine or an alkali carbonate is addedas a acid binder or the reaction is conducted by using at least twoequivalents of the compound (XI) per equivalent of the compound (X).When the product (XII) has a highly reactive halogen atom on itsaromatic ring, it can be further reacted with an alkoxide or amine toconvert it into another compound. The compound of the general formula(IX) can be obtained by reducing the compound (XII) produced asdescribed above by an ordinary process for reducing nitro groups. In apreferred example of the reduction processes, catalytic reduction isconducted in the presence of a palladium/carbon catalyst or thereduction is conducted by using zinc powder and acetic acid. Thecatalytic reduction can be conducted usually in an organic solvent suchas methanol, tetrahydrofuran or dimethylformamide under atmospheric orelevated pressure.

Production process 2 ##STR15## wherein R⁵ _(a), R⁶ _(a), R⁷, A, B, E andL are each as defined above.

The compounds represented by the general formula (IX) can be synthesizedby, for example, a process described in J. Org. Chem., Vol. 24, p. 1314,a process described in J. Heterocycl. Chem., Vol. 20, p. 1339, or aprocess analogous to them. Namely, they can be produced by reacting acompound of the general formula (XIII) with a compound of the generalformula (XI) in the presence of an acid catalyst, such as hydrochloricacid or sulfuric acid in a solvent such as water, ethanol or diethyleneglycol. For increasing the reaction velocity, it is advantageous to heatthe reaction mixture.

Production process 3 ##STR16## wherein R⁵ _(a), R⁶ _(a), R⁷, A, B, E andL are each as defined above.

The compounds represented by the general formula (IX) can be synthesizedby, for example, a process described in J. Chem. Soc. (C) (1970), p.1355 or a process analogous to it. Namely, they can be produced byreacting a compound of the general formula (XIV) with a compound of thegeneral formula (XV) in the presence or absence of an organic solventsuch as dimethylformamide or dioxane at room temperature or underheating.

Production process 4 ##STR17## wherein R⁵ _(a), R⁶ _(a), R⁷, A, B and Eaare each as defined above and Eb represents E defined above in which atleast one G is a protected hydroxyl group.

The compounds represented by the general formula (XVII) can be producedby reacting a compound of the general formula (XVI) with a compound ofthe general formula: X--Y (V), wherein X and Y are as defined above orwith an inorganic acid or organic acid anhydride reactive with thehydroxyl group. The reaction conditions vary depending on the varietiesof X--Y (V) and the anhydride. The reaction solvent is preferably aninert solvent which is not reactive with these compounds, such asdimethylformamide, tetrahydrofuran or dioxane. To increase the reactionvelocity, a base such as sodium hydride, potassium carbonate ortriethylamine may be added to the reaction system or the reaction systemmay be heated. When R⁷ is a hydrogen atom, it is sometimes preferred toprotect it with an ordinary amino-protective group such as abenzyloxycarbonyl group prior to the reaction with X--Y (V) or theanhydride and to remove the protective group after the completion of thereaction. The compounds represented by the general formula (XVIII) canbe produced by reducing the compounds (XVII) produced as described aboveby an ordinary process for reducing nitro groups.

Production process 5 ##STR18## wherein R¹ _(a), R², R³, R⁴, R⁵ _(a), R⁶_(a), A, B and L are each as defined above.

The compounds represented by the general formula (VII) can be producedby reacting a compound of the general formula (XIX) with a compound ofthe general formula (XX). The reaction conditions vary depending on thecompounds. Usually 2 to 4 equivalents of the compound (XX) is preferablyused per equivalent of the sulfonyl halide (XIX). The reaction solventis preferably tetrahydrofuran, dioxane, pyridine, dimethylformamide orthe like. The reaction can be conducted also under hydrous conditions.The reaction usually proceeds at room temperature and, if desired it maybe conducted under cooling or heating.

When the compounds of the present invention are used as medicines, theyare given by oral or parenteral administration. The dosage is notlimited, since it varies depending on the symptoms; age, sex, bodyweight and sensitivity of the patient; administration method; time andinterval of administration; properties, formulation and kind ofpreparation; and the variety of the active ingredient.

The dose, which varies depending on the administration manner, isusually 10 to 6000 mg, preferably about 50 to 4000 mg and, morepreferably, 100 to 3000 mg a day for adult. This dose of the compound isgiven in portions 1 to 3 times a day.

In the production of a solid preparation for oral administration, anexcipient and, if necessary, binder, disintegrator, lubricant, colorant,corrigent, etc., are added to the active ingredient and they are shapedinto tablets, coated tablets, granules, fine granules, powder orcapsules.

Examples of the excipients include lactose, corn starch, white sugar,glucose, sorbitol, crystalline cellulose and silicon dioxide. Examplesof the binders include polyvinyl alcohol, polyvinyl ether,ethylcellulose, methylcellulose, acacia, tragacanth, gelatin, shellac,hydroxypropylcellulose, hydroxypropylmethylcellulose, calcium citrate,dextrin and pectin. Examples of the lubricants include magnesiumstearate, talc, polyethylene glycol, silica and hardened vegetable oils.The colorants are those admitted to be added to medicines. Examples ofthe corrigents include cocoa powder, methanol, aromatic powder,peppermint oil, borneol and cinnamon powder. These tablets and granulesmay be suitably coated with sugar, gelatin or the like, as a matter ofcourse.

In the preparation of an injection, a pH modifier, buffering agent,suspension agent, solubilizer, stabilizer, isotonizer, preservative,etc., are added to the active ingredient to form an intravenous,subcutaneous or intramuscular injection by an ordinary process. Ifnecessary, they are freeze-dried.

Examples of the suspension agents include methylcellulose, Polysorbate80, hydroxyethylcellulose, acacia, tragacanth powder, sodiumcarboxymethylcellulose and polyoxyethylene sorbitan monolaurate.

Examples of the solubilizers include polyoxyethylene-hardened castoroil, Polysorbate 80, nicotinamide, polyoxyethylene sorbitan monolaurate,macrogol and ethyl esters of castor oil fatty acids.

Examples of the stabilizers include sodium sulfite, sodium metasulfiteand ether. Examples of the preservatives include methylp-hydroxybenzoate, ethyl p-hydroxybenzoate, sorbic acid, phenol, cresoland chlorocresol.

EFFECT OF THE INVENTION

The following pharmacological experiments will illustrate the effects ofthe compounds of the present invention.

Experimental Example 1

In vitro antineoplastic test on KB cells (human nasopharyngeal cells):

1.25×10³ (0.1 ml) of KB cells suspended in a RPMI 1640 medium (a productof Nissui Seiyaku Co., Ltd.) containing 20% of bovine fetus serum,penicillin (100 units/ml), streptomycin (100 μg/ml), mercaptoethanol(5×10⁻⁵ M) and sodium pyruvate (1 mM) were placed in each hole of a96-hole flat-bottom microplate and cultured in an incubator containing5% of carbon dioxide at 37° C. for one day.

A compound of the present invention was dissolved in dimethyl sulfoxideto obtain a 20 mg/ml solution, which was diluted to a concentration of100 μg/ml with 0.1% bovine fetus serum/RPMI 1640 culture liquid. Thisconcentration was the maximum one, which was subjected to two-foldserial dilution with 0.1% bovine fetus serum RPMI 1640 culture liquidcontaining 0.5% of dimethyl sulfoxide. It was added to the KB cells ineach hole of the above-described culture plate in an amount of 0.1 mland cultured in an incubator containing 5% of carbon dioxide at 37° C.for three days.

After the completion of the culture, 0.05 ml of MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] solution(3.3 mg/ml) was added to each hole and the culture was conducted for anadditional 1 h. The supernatant liquid was removed from each hole bysuction and a formazan thus formed was dissolved in 0.1 ml of dimethylsulfoxide. The absorbance at 540 nm was determined with a microplatereader to use as an index of a viable count. A percentage inhibition wascalculated according to the following formula and the concentration ofthe test compound for 50% inhibition (IC₅₀) was determined.

Numerical formula 1

    Percentage inhibition (%)=(C-T)/C×100

T: absorbance of the hole containing the test compound

C: absorbance of the hole containing no test compound

Values of IC₅₀ of KB cells in vitro thus determined are given in Table1.

                  TABLE 1                                                         ______________________________________                                               Compound                                                                              IC.sub.50                                                             (Ex. No.)                                                                             (μg/ml)                                                     ______________________________________                                                1      1.5                                                                    2      1.7                                                                    3      0.27                                                                   4      1.9                                                                    5      0.73                                                                   6      0.42                                                                   7      1.0                                                                    8      0.89                                                                   9      0.34                                                                  10      0.21                                                                  11      0.33                                                                  13      2.6                                                                   16      1.5                                                                   17      0.94                                                                  18      0.73                                                                  21      1.1                                                                   27      1.4                                                                   34      0.11                                                                  35      0.45                                                                  36      0.72                                                                  37      1.3                                                                   40      2.1                                                                   42      0.59                                                                  43      0.26                                                                  47      2.6                                                                   52      0.54                                                                  54      0.54                                                                  57      0.17                                                                  58      1.2                                                                   59      0.18                                                                  61      0.83                                                                  62      0.53                                                                  63      0.20                                                                  64      0.55                                                                  65      0.20                                                                  67      1.4                                                                   68      0.17                                                                  70      0.033                                                                 71      0.11                                                                  72      0.012                                                                 76      0.13                                                                  82      0.026                                                                 85      0.010                                                                 88      0.010                                                                 91      0.079                                                                 94      0.064                                                                 95      0.045                                                                 97      0.15                                                                  98      0.079                                                                 101     0.10                                                                  104     0.099                                                                 106     0.30                                                           ______________________________________                                    

Experimental Example 2

In vivo antineoplastic test on colon 38 (cancer of the colon of mice):

About 75 mg of colon 38 was subcutaneously transplanted in the side ofthe body of each of 7-week old female BDF₁ mice. A compound of thepresent invention was suspended in 0.5% methylcellulose and oraladministration of a predetermined amount of the suspension once a daywas started on the next day and continued for 8 days. 0.5%methylcellulose was orally given to a control group. The control groupconsisted of 10 mice and the group to which the medicine was givenconsisted of 6 mice.

21 days after the transplantation, the tumors were taken out andweighed. The tumor growth inhibition ratio of the group to which themedicine was given to the control group was determined according to thefollowing formula:

Numerical formula 2

    Growth inhibition ratio (%) (C-T)/C×100

T: average weight of tumor in the group to which the test compound wasgiven

C: average weight of tumor in the control group

The results of the experiments are given in Table 2.

                  TABLE 2                                                         ______________________________________                                                            Growth    Survival rate on the                            Compound                                                                              Dose        inhibition                                                                              day of judgement                                (Ex. No.)                                                                             (mg/kg/day) ratio     (the 21st day)                                  ______________________________________                                        1       100         80        100                                             2       100         69        100                                             3       100         98        100                                             4       100         99        100                                             6       100         98        100                                             7        50         61        100                                             70       50         63        100                                             ______________________________________                                    

Experimental Example 3: Toxicity tests

A 0.5% suspension of a compound of Example 3, 4 or 6 in methylcellulosewas given to a group of five 7-week old female BDF₁ mice once and theviability of them was observed for 7 days after the administration. Nomouse died, even with 1651 mg/kg of the compound.

It is apparent from the above Experimental Examples that the compoundsof the present invention exhibit a quite excellent antineoplasticeffect. In addition, the compounds of the present invention have such ahigh safety that they are useful as a remedy for malignant tumors, i.e.as an antineoplastic agent.

EXAMPLES

The following Production Examples will illustrate the processes forproducing the starting compounds of the compounds of the presentinvention and the following Examples will illustrate the typicalcompounds of the present invention, which by no means limit theinvention.

Production Example 1

2-Anilino-3-nitropyridine: ##STR19##

A mixture of 11.21 g (70 mmol) of 2-chloro-3-nitropyridine and 19.56 g(210 mmol) of aniline was heated under stirring at 100° C. for 1 h. Thereaction liquid was cooled to room temperature and dissolved in ethylacetate. The solution was washed with an aqueous citric acid solutionand then with water. After drying over magnesium sulfate, the solventwas distilled off under reduced pressure and the residue wasrecrystallized from ethyl acetate/n-hexane to obtain 13.7 g of the titlecompound.

Melting point: 73° to 74° C.

FAB mass spectrometry m/z: 216 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 6.84 (1H, dd, J=8.4, 4.4 Hz), 7.18-7.22 (1H,m), 7.37-7.43 (2H, m), 7.62-7.68 (2H, m), 8.49 (1H, dd, J=4.4, 2.0 Hz),8.53 (1H, dd, J=8.4, 2.0 Hz), 10.12 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.9 N.sub.3 O.sub.2 :                                C            H      N                                             ______________________________________                                        Calculated: 61.39        4.22   19.53                                         Found:      61.49        4.34   19.23                                         ______________________________________                                    

Production Example 2

3-Amino-2-anilinopyridine: ##STR20##

6.8 g (31.6 mmol) of the compound produced in Production Example 1 wasdissolved in a mixture of 40 ml of tetrahydrofuran and 6 ml of methanol.Palladium/carbon was added to the solution to conduct hydrogenation atroom temperature under atmospheric pressure. The palladium/carbon wasremoved by filtration, the solvent was distilled off under reducedpressure and the residue was recrystallized from ethyl acetate/n-hexaneto obtain 5.5 g of the title compound.

Melting point: 143° to 144° C.

FAB mass spectrometry m/z: 186 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 4.95-5.10 (2H, br), 6.61 (1H, dd, J=7.2, 4.8Hz), 6.80-6.86 (1H, m), 6.90 (1H, dd, J=7.2, 1.6 Hz), 7.18-7.24 (2H, m),7.49 (1H, dd, J=4.8, 1.6 Hz), 7.60-7.65 (2H, m), 7.69 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.11 N.sub.3 :                                       C            H      N                                             ______________________________________                                        Calculated: 71.33        5.99   22.69                                         Found:      71.49        6.04   22.59                                         ______________________________________                                    

Production Example 3

4-[(3-Nitro-2-pyridyl)amino]phenol ##STR21##

8.17 g (50 mmol) of 2-chloro-3-nitropyridine and 16.70 g (150 mmol) ofp-aminophenol were added to 50 ml of dimethylformamide and the mixturewas stirred at 100° C. for 40 min. The solvent was distilled off underreduced pressure, the same treatment as that of Production Example 1 wasrepeated and the product was recrystallized from ethanol to obtain 9.4 gof the title compound.

Melting point: 143° to 144° C.

FAB mass spectrometry m/z: 231 (M⁺)

¹ H-NMR (CDCl₃) δ (ppm): 5.23 (1H, s), 6.79 (1H, dd, J=4.8, 8.4 Hz),6.84 (2H, d, J=8.8 Hz), 7.41 (2H, d, J=8.8 Hz), 8.44 (1H, dd, J=1.6, 4.8Hz), 8.52 (1H, dd, J=1.6, 8.4 Hz), 9.94 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.9 N.sub.3 O.sub.3 :                                C            H      N                                             ______________________________________                                        Calculated: 57.14        3.92   18.18                                         Found:      57.15        3.97   18.14                                         ______________________________________                                    

Production Example 4

4-[(3-Amino-2-pyridyl)amino]phenol ##STR22##

9.25 g (40 mmol) of the compound produced in Production Example 3 wascatalytically reduced and treated in the same manner as that ofProduction Example 2 and the product was recrystallized from methanol toobtain 7.8 g of the title compound.

Melting point: 205° to 207° C.

FAB mass spectrometry m/z: 202 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 4.94 (2H, br-s), 6.50 (1H, dd, J=4.8, 7.6Hz), 6.66 (2H, d, J=8.8 Hz), 6.82 (1H, dd, J=1.6, 7.6 Hz), 7.38 (1H, s),7.39 (2H, d, J=8.8 Hz), 7.40 (1H, dd, J=1.6, 4.8 Hz), 8.85 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.11 N.sub.3 O:                                      C            H      N                                             ______________________________________                                        Calculated: 65.66        5.51   20.88                                         Found:      65.85        5.51   20.84                                         ______________________________________                                    

Production Example 5

3-[(3-Nitro-2-pyridyl)amino)]phenol: ##STR23##

Melting point: 148° to 149° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 232 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 5.31 (1H, br-s), 6.65 (1H, dd, J=8.0, 2.4 Hz),6.85 (1H, dd, J=8.4, 4.8 Hz), 7.08 (1H, dd, J=8.0, 2.4 Hz), 7.24 (1H, t,J=8.0 Hz), 7.37 (1H, t, J=2.4 Hz), 8.49 (1H, dd, J=4.8, 1.6 Hz), 8.54(1H, dd, J=8.4, 1.6 Hz), 10.11 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.9 N.sub.3 O.sub.3 :                                C            H      N                                             ______________________________________                                        Calculated: 57.14        3.92   18.17                                         Found:      57.33        4.03   18.18                                         ______________________________________                                    

Production Example 6

3-[(3-Amino-2-pyridyl)amino)]phenol: ##STR24##

Melting point: gradual decomposition observed at 198° C. (recrystallizedfrom ethanol)

FAB mass spectrometry m/z: 202 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 5.04 (2H, s), 6.24-6.28 (1H, m), 6.60 (1H,dd, J=7.6, 4.8 Hz), 6.89 (1H, dd, J=7.6, 1.6 Hz), 6.97-6.99 (2H, m),7.23 (1H, br-s), 7.50 (1H, dd, J=4.8, 1.6 Hz), 7.57 (1H, s), 9.10 (1H,s)

    ______________________________________                                        Elementary analysis for C.sub.11 H.sub.11 N.sub.3 O:                                      C            H      N                                             ______________________________________                                        Calculated: 65.66        5.51   20.88                                         Found:      65.92        5.58   20.86                                         ______________________________________                                    

Production Example 7

2-[(4-Methoxymethyloxyphenyl)amino]-3-nitropyridine ##STR25##

8.4 g (54.8 mmol) of 4-methoxymethyloxyaniline and 7.5 g (49 mmol) of2-chloro-3-nitropyridine were dissolved in 35 ml of dimethylformamide.7.6 g (55 mmol) of anhydrous potassium carbonate was added to thesolution. The resulting solution was heated under stirring at 100° C.for 4 h. The reaction liquid was cooled to room temperature and aninsoluble matter thus formed was removed by filtration. The solvent wasdistilled off under reduced pressure and the residue was dissolved inethyl acetate. The solution was washed with an aqueous citric acidsolution and then with water. After drying over magnesium sulfate, thesolvent was distilled off under reduced pressure and the residue wasrecrystallized from ethanol to obtain 9.68 g of the title compound.

Melting point: 80° to 81° C.

FAB mass spectrometry m/z: 275 (M⁺)

¹ H-NMR (CDCl₃) δ (ppm): 3.50 (3H, s), 5.19 (2H, s), 6.79 (1H, dd,J=4.4, 8.4 Hz), 7.08 (2H, d, J=8.8 Hz), 7.50 (2H, d, J=8.8 Hz), 8.45(1H, dd, J=1.6, 4.4 Hz), 8.51 (1H, dd, J=1.6, 8.4 Hz), 9.99 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.13 H.sub.13 N.sub.3 O.sub.4 :                               C            H      N                                             ______________________________________                                        Calculated: 56.73        4.76   15.27                                         Found:      57.06        4.83   15.02                                         ______________________________________                                    

Production Example 82-[N-Benzyloxycarbonyl-N-(4-methoxymethyloxyphenyl)amino]-3-nitropyridine:##STR26##

4.0 g (14.5 mmol) of the compound produced in Production Example 7 wasdissolved in 70 ml of dimethylformamide. 720 mg (18 mmol) of sodiumhydride (60%) was added to the solution. 3.2 ml (22.4 mmol) of benzylchloroformate was added dropwise thereto under stirring at roomtemperature. After stirring at room temperature overnight, the solventwas distilled off under reduced pressure. Ethyl acetate and water wereadded to the residue and the ethyl acetate layer was separated. Afterwashing the separated layer with water followed by drying (overmagnesium sulfate), concentration and purification by silica gel columnchromatography, 4.5 g of an oily title compound was obtained.

¹ H-NMR (CDCl₃) δ (ppm): 3.47 (3H, s), 5.17 (4H, s+s), 7.06 (2H, d,J=8.8 Hz), 7.22-7.26 (2H, m), 7.29-7.33 (4H, m), 7.37 (2H, d, J=8.8 Hz),8.29 (1H, d, J=8.0 Hz), 8.56 (1H, d, J=4.4 Hz)

Production Example 9

4-[N-Benzyloxycarbonyl-N-(3-nitro-2-pyridyl)amino]phenol: ##STR27##

500 mg (1.22 mmol) of the compound produced in Production Example 8 wasdissolved in a mixture of 6 ml of tetrahydrofuran and 1 ml of water. 2ml of concentrated hydrochloric acid was added to the solution. Afterthe mixture was stirred at room temperature overnight, the solvent wasdistilled off under reduced pressure. Ethyl acetate and a saturatedaqueous sodium hydrogencarbonate solution were added to the residue andthe ethyl acetate layer thus formed was separated. After washing theseparated layer with water followed by drying (over magnesium sulfate)and concentration, 445 mg of the title compound was obtained.

¹ H-NMR (DMSO-d₆) δ (ppm): 5.11 (2H, s), 6.77 (2H, d, J=8.8 Hz),7.18-7.24 (4H, m), 7.31-7.34 (3H, m), 7.58 (1H, dd, J=4.8, 8.0 Hz), 8.51(1H, dd, J=1.6, 8.0 Hz), 8.66 (1H, dd, J=1.6, 4.8 Hz), 9.64 (1H, s)

Production Example 10

4-[(3-Amino-2-pyridyl)amino]phenyl tert-butoxycarbonylaminoacetate:##STR28##

440 mg (1.2 mmol) of the compound produced in Production Example 9, 250mg (1.43 mmol) of N-(tert-butoxycarbonyl)glycine and 25 mg (0.2 mmol) of4-dimethylaminopyridine were dissolved in 10 ml of pyridine. 290 mg(1.41 mmol) of 1,3-dicyclohexylcarbodiimide was added to the solution.After stirring at room temperature overnight, the solvent was distilledoff under reduced pressure. Ethyl acetate was added to the residue, theinsoluble matter was removed by filtration and the solvent was distilledoff under reduced pressure. The residue was purified according to silicagel column chromatography and the resulting compound was catalyticallyreduced in the presence of a palladium/carbon catalyst by an ordinaryprocess. After the removal of the catalyst by filtration followed byconcentration, the residue was purified by silica gel columnchromatography to obtain 236 mg of the title compound.

¹ H-NMR (DMSO-d₆) δ (ppm): 1.41 (9H, s), 3.93 (2H, d, J=6.0 Hz), 5.05(2H, br-s), 6.62 (1H, dd, J=4.8, 7.2 Hz), 6.90 (1H, dd, J=1.6, 7.2 Hz),6.96 (2H, d, J=9.2 Hz), 7.37 (1H, br-t, J=6.4 Hz), 7.49 (1H, dd, J=1.6,4.8 Hz), 7.64 (2H, d, J=9.2 Hz), 7.79 (1H, s)

Production Example 11

4-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]phenyl-2,3,4,6-tetra-O-acetyl-β-D-glucopyranoside:##STR29##

3.753 g (10.10 mmol) of the compound produced in Example 6 and 3.959 g(10.14 mmol) of β-D-glucose pentacetate were suspended in 200 ml of1,2-dichloroethane. 30 ml of a 1.0M solution of tin tetrachloride indichloromethane was added dropwise to the suspension under stirring andunder cooling with ice in a nitrogen atmosphere. After stirring undercooling with ice for 2 h and then at room temperature for 4 days, thereaction mixture was added to ice/water containing 16 g of sodiumhydrogencarbonate. The organic solvent was distilled off under reducedpressure. Ethyl acetate was added to the residue and the insolublematter thus formed was removed by filtration. The ethyl acetate layerwas separated, washed with water, dried, concentrated and purified bysilica gel column chromatography to obtain 2.47 g of the title compound.

¹ H-NMR (CDCl₃) δ (ppm): 2.04 (3H, s), 2.05 (3H, s), 2.08 (3H, s), 2.10(3H, s), 3.80-3.86 (1H, m), 3.84 (3H, s), 4.17 (1H, dd, J=12.4, 2.4 Hz),4.30 (1H, dd, J=12.4, 5.6 Hz), 4.99 (1H, d, J=7.6 Hz), 5.16 (1H, t,J=9.6 Hz), 5.23-5.32 (2H, m), 6.37 (1H, br-s), 6.54 (1H, dd, J=4.8, 7.6Hz), 6.84 (1H, dd, J=1.6, 7.6 Hz), 6.92 (2H, d, J=8.8 Hz), 6.94 (2H, d,J=8.8 Hz), 7.32 (1H, br-s), 7.38 (2H, d, J=8.8 Hz), 7.69 (2H, d, J=8.8Hz), 8.07 (1H, dd, J=1.6, 4.8 Hz)

Production Example 12

N-(2-Aminophenyl)-4-methoxybenzenesulfonamide: ##STR30##

33.1 g (0.3 mol) of 1,2-phenylenediamine was dissolved in 200 ml ofdioxane. A solution of 20.87 g (0.1 mol) of 4-methoxybenzenesulfonylchloride in 110 ml of dioxane was added thereto under stirring. Theresulting mixture was stirred at room temperature overnight. 12.1 g(0.12 mol) of triethylamine was added thereto. After concentrationfollowed by addition of an aqueous citric acid solution and ethylacetate, the organic layer was separated, concentrated and purified bysilica gel column chromatography to obtain 27.1 g of the title compound.

Melting point: 141° to 142° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 279 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.81 (3H, s), 4.91 (2H, br-s), 6.37 (1H, td,J=1.6, 7.2, 8.0 Hz), 6.60 (1H, dd, J=1.6, 8.0 Hz), 6.66 (1H, dd, J=1.6,8.0 Hz), 6.86 (1H, td, J=1.6, 7.2, 8.0 Hz), 7.03 (2H, d, J=8.8 Hz), 7.61(2H, d, J=8.8 Hz), 9.07 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.13 H.sub.14 N.sub.2 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 56.10        5.07   10.07                                         Found:      55.98        5.03   10.00                                         ______________________________________                                    

Production Example 13

N-(2-Aminophenyl)-4-nitrobenzenesulfonamide: ##STR31##

The title compound was produced in the same manner as that of ProductionExample 12.

Melting point: 190° to 191° C. (recrystallized from benzene)

FAB mass spectrometry m/z: 294 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ(ppm): 4.90 (2H, br-s), 6.42 (1H, dt, J=1.6, 8.0 Hz),6.61 (1H, dd, J=1.6, 8.0 Hz), 6.71 (1H, dd, J=1.6, 8.0 Hz), 6.91 (1H,dt, J=1.6, 8.0 Hz), 7.91 (2H, d, J=8.8 Hz), 8.36 (2H, d, J=8.8 Hz)

    ______________________________________                                        Elementary analysis for C.sub.12 H.sub.11 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 49.14        3.78   14.33                                         Found:      49.38        3.82   14.13                                         ______________________________________                                    

Production Example 14

N-(2-Amino-3-methylphenyl)-4-methoxybenzenesulfonamide: ##STR32##

The title compound was produced in the same manner as that of ProductionExample 12.

Melting point: 177° to 178° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 293 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.03 (3H, s), 3.81 (3H, s), 4.75 (2H, br-s),6.30 (1H, t, J=7.6 Hz), 6.44 (1H, dd, J=1.2, 7.6 Hz), 6.79 (1H, dd,J=1.2, 7.6 Hz), 7.04 (2H, d, J=8.8 Hz), 7.61 (2H, d, J=8.8 Hz)

    ______________________________________                                        Elementary analysis for C.sub.14 H.sub.16 N.sub.2 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 57.52        5.52   9.58                                          Found:      57.76        5.51   9.57                                          ______________________________________                                    

Example 1

N-(2-Anilino-3-pyridyl)-p-toluenesulfonamide: ##STR33##

3.7 g (20 mmol) of the compound produced in Production Example 2 wasdissolved in 30 ml of pyridine. 30 ml of a solution of 3.81 g (20 mmol)of p-toluenesulfonyl chloride in tetrahydrofuran was added in portionsto the solution under stirring at room temperature. After stirringovernight, the solvent was distilled off under reduced pressure and theresidue was dissolved in ethyl acetate. The solution was washed withwater and dried over magnesium sulfate. The solvent was distilled offunder reduced pressure and the residue was recrystallized from ethanolto obtain 5.2 g of the title compound.

Melting point: 164° to 165° C.

FAB mass spectrometry m/z: 340 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.23 (3H, s), 6.73 (1H, dd, J=4.8, 7.6 Hz),6.86-6.92 (1H, m), 7.18-7.24 (2H, m), 7.24 (2H, d, J=8.0 Hz), 7.27 (1H,dd, J=7.6, 1.6 Hz), 7.36-7.42 (2H, m), 7.54 (2H, d, J=8.0 Hz), 7.86 (1H,s), 7.99 (1H, dd, J=4.8, 1.6 Hz), 9.62 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 63.70        5.05   12.38                                         Found:      63.77        5.11   12.28                                         ______________________________________                                    

Example 2

N-(2-Anilino-3-pyridyl)-4-ethylbenzenesulfonamide: ##STR34##

3.11 g (16.8 mmol) of the compound produced in Production Example 2 wasreacted with 3.43 g (16.8 mmol) of p-ethylbenzenesulfonyl chloride andthe product was treated in the same manner as that of Example 1 toobtain 5.0 g of the title compound.

Melting point: 138° to 139° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 354 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.02 (3H, t), 2.50 (2H, q), 6.72 (1H, dd,J=5.2, 8.0 Hz), 6.83-6.89 (1H, m), 7.14-7.20 (2H, m), 7.24 (2H, d, J=8.4Hz), 7.29 (1H, dd, J=8.0, 1.8 Hz), 7.32-7.37 (2H, m), 7.54 (2H, d, J=8.4Hz), 7.80 (1H, s), 7.97 (1H, dd, J=5.2, 1.8 Hz), 9.60 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 64.57        5.42   11.89                                         Found:      64.89        5.33   12.00                                         ______________________________________                                    

Example 3

N-(2-Anilino-3-pyridyl)-4-methoxybenzenesulfonamide: ##STR35##

1.39 g (7.5 mmol) of the compound produced in Production Example 2 wasreacted with 1.55 g (7.5 mmol) of p-methoxybenzenesulfonyl chloride andthe product was treated in the same manner as that of Example 1 toobtain 2.6 g of the title compound.

Melting point: 172° to 173° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 356 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.68 (3H, s), 6.71 (1H, dd, J=7.6, 5.0 Hz),6.84-6.90 (1H, m), 6.92 (2H, d, J=9.2 Hz), 7.15-7.22 (2H, m), 7.25 (1H,dd, J=7.6, 1.2 Hz), 7.36-7.42 (2H, m), 7.57 (2H, d, J=9.2 Hz), 7.86 (1H,s), 7.97 (1H, dd, J=5.0, 1.2 Hz), 9.51 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 60.83        4.82   11.82                                         Found:      61.02        4.69   11.86                                         ______________________________________                                    

Example 4

4-Methoxy-N-[2-[(4-methoxyphenyl)amino]-3-pyridyl]-benzenesulfonamide:##STR36##

The title compound was obtained in the same manner as that of Example 1.

Melting point: 145° to 147° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 3.79 (3H, s), 3.85 (3H, s), 6.16 (1H, br-s),6.52 (1H, dd, J=4.8, 7.6 Hz), 6.85 (3H, d, J=8.8 Hz), 6.93 (2H, d, J=8.8Hz), 7.12 (1H, br-s), 7.32 (2H, d, J=8.8 Hz), 7.69 (2H, d, J=8.8 Hz),8.07 (1H, dd, J=1.6, 4.8 Hz)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.21        4.97   10.90                                         Found:      59.26        5.05   10.75                                         ______________________________________                                    

Example 5

4-Methoxy-N-[2-[(4-methoxymethyloxyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR37##

The title compound was produced in the same manner as that of Example 1.

Melting point: 118° to 119° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 416 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 3.48 (3H, s), 3.83 (3H, s), 5.13 (2H, s), 6.45(1H, br-s), 6.52 (1H, dd, J=4.4, 7.6 Hz), 6.87 (1H, dd, J=1.6, 7.6 Hz),6.92 (2H, d, J=8.8 Hz), 6.97 (2H, d, J=8.8 Hz), 7.16 (1H, br-s), 7.31(2H, d, J=8.8 Hz), 7.69 (2H, d, J=8.8 Hz), 8.07 (1H, d)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.21 N.sub.3 O.sub.5 S:                              C            H      N                                             ______________________________________                                        Calculated: 57.82        5.09   10.11                                         Found:      57.93        5.02    9.84                                         ______________________________________                                    

Example 6

N-[2-[(4-Hydroxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR38##

1.01 g (5 mmol) of the compound produced in Production Example 4 wasreacted with 1.05 g (5 mmol) of p-methoxybenzenesulfonyl chloride andthe product was treated in the same manner as that of Example 1 toobtain 1.43 g of the title compound.

Melting point: 178° to 179° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 372 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.60 (1H, dd, J=4.8, 7.6 Hz),6.63 (2H, d, J=8.8 Hz), 6.98 (2H, d, J=8.8 Hz), 7.14 (2H, d, J=8.8 Hz),7.18 (1H, dd, J=1.6, 7.6 Hz), 7.58 (1H, br-s), 7.60 (2H, d, J=8.8 Hz),7.88 (1H, dd, J=1.6, 4.8 Hz), 8.97 (1H, s), 9.44 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 58.21        4.61   11.31                                         Found:      58.40        4.67   11.38                                         ______________________________________                                    

2.0 g of the title compound was dissolved in 50 ml of tetrahydrofuran.0.5 ml of concentrated hydrochloric acid was added to the solution andthe resulting solution was concentrated to dryness. The residue wasrecrystallized from methanol to obtain 1.9 g of hydrochloride of thetitle compound.

Melting point: gradual decomposition observed at 225° C.

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.4 S.HCl:                          C            H      N                                             ______________________________________                                        Calculated: 53.01        4.45   10.30                                         Found:      52.97        4.33   10.19                                         ______________________________________                                    

Example 7

4-Methoxy-N-[2-[(4-pyridyl)amino]-3-pyridyl]benzenesulfonamide:##STR39##

The title compound was produced in the same manner as that of Example 1.

Melting point: 172° to 173° C. (recrystallized from ethyl acetate)

FAB mass spectrometry m/z: 357 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.67 (3H, s), 6.86-6.91 (3H, m), 7.37 (1H,dd, J=1.6, 7.6 Hz), 7.48 (2H, d, J=5.6 Hz), 7.54 (2H, d, J=9.2 Hz), 8.04(1H, dd, J=1.6, 4.8 Hz), 8.26 (2H, d, J=5.6 Hz), 8.59 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.16 N.sub.4 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 57.29        4.53   15.72                                         Found:      57.37        4.56   15.66                                         ______________________________________                                    

Example 8

4-Methoxy-N-[2-[(4-methylphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR40##

The title compound was produced in the same manner as that of Example 1.

Melting point: 188° to 189° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.21 (3H, s), 3.69 (3H, s), 6.66 (1H, dd,J=6.4, 2.4 Hz), 6.92 (2H, d, J=7.2 Hz), 6.99 (2H, d, J=7.6 Hz), 7.21(1H, dd, J=6.4, 1.6 Hz), 7.27 (2H, d, J=7.2 Hz), 7.56 (2H, d, J=7.6 Hz),7.75 (1H, s), 7.93 (1H, dd, J=2.4, 1.6 Hz), 9.48 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 61.77        5.18   11.38                                         Found:      61.82        5.21   11.30                                         ______________________________________                                    

Example 9

N-[2-[(2-Fluorophenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR41##

The title compound was produced in the same manner as that of Example 1.

Melting point: 148° to 150° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 374 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.72 (3H, s), 6.76 (1H, dd, J=7.6, 4.8 Hz),6.90-6.98 (3H, m), 7.05 (1H, td, J=8.0, 0.8 Hz), 7.13-7.20 (2H, m), 7.57(2H, d, J=8.8 Hz), 7.82 (1H, d, J=2.8 Hz), 7.95 (1H, t, J=8.0 Hz), 8.01(1H, dd, J=4.8, 1.6 Hz), 9.76 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 FN.sub.3 O.sub.3 S:                             C            H      N                                             ______________________________________                                        Calculated: 57.90        4.32   11.25                                         Found:      57.93        4.57   10.98                                         ______________________________________                                    

Example 10

N-[2-[(3-Fluorophenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR42##

The title compound was produced in the same manner as that of Example 1.

Melting point: 180° to 181° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 374 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.69 (3H, s), 6.67 (1H, td, J=8.4, 2.0 Hz),6.81 (1H, dd, J=7.6, 4.8 Hz), 6.92 (2H, d, J=8.8 Hz), 7.09 (1H, dd,J=8.4, 2.0 Hz), 7.22 (1H, dt, J=8.4, 6.8 Hz), 7.31 (1H, dd, J=7.6, 1.6Hz), 7.49 (1H, dt, J=2.0, 12.4 Hz), 7.56 (2H, d, J=8.8 Hz), 8.05 (1H,dd, J=4.8, 1.6 Hz), 8.12 (1H, s), 9.52 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 FN.sub.3 O.sub.3 S:                             C            H      N                                             ______________________________________                                        Calculated: 57.90        4.32   11.25                                         Found:      57.89        4.42   11.16                                         ______________________________________                                    

Example 11N-[2-[(4-Fluorophenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR43##

The title compound was produced in the same manner as that of Example 1.

Melting point: 196° to 197° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 374 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 6.72 (1H, dd, J=4.8, 7.6 Hz),6.95 (2H, d, J=8.8 Hz), 7.04 (2H, t, J=8.8 Hz), 7.25 (1H, dd, J=1.6, 7.6Hz), 7.42 (2H, m), 7.58 (2H, d, J=8.8 Hz), 7.95 (1H, br-s), 7.98 (1H,dd, J=1.6, 4.8 Hz), 9.48 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 FN.sub.3 O.sub.3 S:                             C            H      N                                             ______________________________________                                        Calculated: 57.90        4.32   11.25                                         Found:      57.83        4.32   11.21                                         ______________________________________                                    

Example 12 N-(2-Anilino-3-pyridyl)benzenesulfonamide: ##STR44##

The title compound was produced in the same manner as that of Example 1.

Melting point: 148° to 150° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 326 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.73 (1H, dd, J=7.6, 4.8 Hz), 6.87-6.93 (1H,m), 7.18-7.24 (2H, m), 7.25 (1H, dd, J=7.6, 1.6 Hz), 7.41-7.47 (2H, m),7.47-7.51 (2H, m), 7.51-7.57 (1H, m) 7.67-7.72 (2H, m), 7.90 (1H, s),7.99 (1H, dd, J=4.8, 1.6 Hz), 9.73 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.15 N.sub.3 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 62.75        4.65   12.91                                         Found:      63.03        4.74   12.67                                         ______________________________________                                    

Example 13

4-Methoxy-N-[2-[(3-methoxyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR45##

The title compound was produced in the same manner as that of Example 1.

Melting point: 161° to 162° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.67, 3.70 (3H×2), 6.47 (1H, dd, J=8.0, 2.0Hz), 6.73 (1H, dd, J=8.0, 4.8 Hz), 6.93 (2H, d, J=8.8 Hz), 6.97 (1H, dd,J=8.0, 2.0 Hz), 7.10 (1H, t, J=8.0 Hz), 7.13 (1H, t, J=2.0 Hz), 7.29(1H, dd, J=8.0, 1.6 Hz), 7.59 (2H, d, J=8.8 Hz), 7.89 (1H, s), 8.01 (1H,dd, J=4.8, 1.6 Hz), 9.55 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.21        4.97   10.90                                         Found:      59.14        4.96   10.74                                         ______________________________________                                    

Example 14

4-Hydroxy-N-[2-[(4-hydroxyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR46##

The compound produced in Example 4 was dissolved in DMF and fiveequivalents of sodium methanethiolate was added to the solution. Theresulting solution was heated at 100° C. and treated to obtain the titlecompound.

Melting point: 252° to 257° C. (decomp.) (recrystallized fromethanol/water)

FAB mass spectrometry m/z: 358 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.60 (1H, dd, J=7.6, 4.8 Hz), 6.65 (2H, d,J=8.8 Hz), 6.81 (2H, d, J=8.8 Hz), 7.14 (1H, dd, J=7.6, 1.6 Hz), 7.19(2H, d, J=8.8 Hz), 7.52 (2H, d, J=8.8 Hz), 7.61 (1H, s), 7.87 (1H, dd,J=4.8, 1.6 Hz), 9.01 (1H, s), 9.39 (1H, s), 10.42 (1H, s)

Example 15

N-[2-[(3,4-Dimethoxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR47##

The title compound was produced in the same manner as that of Example 1.

Melting point: 126° to 127° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 415 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.72, 3.73 (3H×3), 6.66 (1H, dd, J=8.0, 3.6Hz), 6.81 (1H, d, J=8.8 Hz), 6.96-6.98 (3H, m), 7.02 (1H, s), 7.21 (1H,dd, J=8.0, 1.2 Hz), 7.60 (2H, d, J=8.0 Hz), 7.73 (1H, s), 7.95 (1H, dd,J=3.6, 1.2 Hz), 9.45 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.21 N.sub.3 O.sub.5 S:                              C            H      N                                             ______________________________________                                        Calculated: 57.82        5.10   10.12                                         Found:      57.73        5.10   10.07                                         ______________________________________                                    

Example 16

4-Methoxy-N-[2-[(2-methoxyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR48##

The title compound was produced in the same manner as that of Example 1.

Melting point: 159° to 160° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.78 (3H, s), 3.89 (3H, s), 6.69 (1H, dd,J=7.6, 4.8 Hz), 6.87-6.90 (2H, m), 6.96-7.01 (2H, m), 7.05 (2H, d, J=8.8Hz), 7.66 (2H, d, J=8.8 Hz), 8.08 (1H, dd, J=4.8, 1.6 Hz), 8.10 (1H, s),8.40 (1H, dd, J=6.4, 2.8 Hz), 9.78 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.21        4.97   10.90                                         Found:      59.16        5.01   10.96                                         ______________________________________                                    

Example 17

4-Methoxy-N-[2-[(3-methyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR49##

The title compound was produced in the same manner as that of Example 1.

Melting point: 147° to 148° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.26 (3H, s), 3.71 (3H, s), 6.71-6.73 (2H,m), 6.95 (2H, d, J=7.6 Hz), 7.09 (1H, t, J=7.6 Hz), 7.16 (1H, s),7.25-7.27 (2H, m), 7.59 (2H, d, J=7.6 Hz), 7.90 (1H, s), 8.00 (1H, dd,J=2.8, 1.6 Hz), 9.53 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 61.77        5.18   11.38                                         Found:      61.79        5.18   11.46                                         ______________________________________                                    

Example 18

4-Methoxy-N-[2-[(2-methylphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR50##

The title compound was produced in the same manner as that of Example 1.

Melting point: 147° to 148° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.06 (3H, s), 3.77 (3H, s), 6.65 (1H, dd,J=7.6, 4.8 Hz), 6.92 (1H, t, J=7.6 Hz), 7.03 (2H, d, J=8.8 Hz), 7.09(1H, t, J=7.6 Hz), 7.11-7.15 (2H, m), 7.53 (1H, s), 7.55 (1H, d, J=7.6Hz), 7.63 (2H, d, J=8.8 Hz), 7.91 (1H, dd, J=4.8, 1.6 Hz), 9.67 (1H,s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 61.77        5.18   11.38                                         Found:      61.80        5.17   11.40                                         ______________________________________                                    

Example 19

N-(2-Anilino-3-pyridyl)-4-hydroxybenzenesulfonamide: ##STR51##

The title compound was produced by treating the compound of Example 3 inthe same manner as that of Example 14.

Melting point: 226° to 228° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 342 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.71 (1H, dd, J=7.6, 4.8 Hz), 6.79 (2H, d,J=8.8 Hz), 6.88-6.94 (1H, m), 7.21 (1H, dd, J=7.6, 1.6 Hz), 7.21-7.27(2H, m), 7.46-7.51 (2H, m), 7.52 (2H, d, J=8.8 Hz), 7.92 (1H, s), 7.97(1H, dd, J=4.8, 1.6 Hz), 9.50 (1H, s), 10.40 (1H, s)

Example 20

N-(2-Anilino-3-pyridyl)-4-nitrobenzenesulfonamide: ##STR52##

The title compound was produced in the same manner as that of Example 1.

Melting point: 191° to 192° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 371 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.80-6.83 (2H, m), 7.12 (2H, t, J=8.4 Hz),7.25 (2H, d, J=8.4 Hz), 7.40 (1H, dd, J=1.6, 7.6 Hz), 7.83 (3H, d, J=8.8Hz), 8.07 (1H, br-s), 8.19 (2H, d, J=8.8 Hz), 9.91 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.14 N.sub.4 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 55.13        3.81   15.13                                         Found:      55.17        3.97   14.77                                         ______________________________________                                    

Example 21

4-Amino-N-(2-anilino-3-pyridyl)benzenesulfonamide: ##STR53##

The title compound was produced by catalytically reducing the compoundof Example 20 in the presence of a palladium/carbon catalyst by anordinary process.

Melting point: 228° to 230° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 341 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 5.99 (2H, br-s), 6.50 (2H, d, J=8.8 Hz), 6.70(1H, dd, J=4.4, 7.6 Hz), 6.91 (1H, td, J=0.8, 7.2 Hz), 7.18 (1H, dd,J=1.6, 7.6 Hz), 7.24 (2H, t, J=7.6 Hz), 7.33 (2H, d, J=8.8 Hz), 7.53(2H, dt, J=1.2, 7.6 Hz), 7.95 (2H, br-s), 9.31 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.16 N.sub.4 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.98        4.74   16.46                                         Found:      60.08        4.67   16.23                                         ______________________________________                                    

Example 22

N-(2-Anilino-3-pyridyl)-3,4-dimethoxybenzenesulfonamide: ##STR54##

The title compound was produced in the same manner as that of Example 1.

Melting point: 171° to 172° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.64 (3H, s), 3.69 (3H, s), 6.75 (1H, dd,J=4.8 7.6 Hz), 6.88 (1H, t, J=7.6 Hz), 6.93 (1H, d, J=8.8 Hz), 7.10 (1H,d, J=2.0 Hz), 7.17-7.22 (3H, m), 7.32 (1H, d, J=7.6 Hz), 7.39 (2H, d,J=8.0 Hz), 7.89 (1H, br-s), 8.00 (1H, d, J=4.8 Hz), 9.48 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.21        4.97   10.90                                         Found:      59.22        4.91   10.63                                         ______________________________________                                    

Example 23

4-Hydroxy-N-[2-[(4-methoxyphenyl)amino]-3-pyridyl]benzenesulfonamide:##STR55##

The title compound was produced by the same treatment as that of Example14.

Melting point: 214° to 216° C. (recrystallized from ethanol/water)

FAB mass spectrometry m/z: 372 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 6.63 (1H, dd, J=7.6, 4.8 Hz),6.80 (2H, d, J=8.8 Hz), 6.82 (2H, d, J=8.8 Hz), 7.16 (1H, dd, J=7.6, 1.6Hz), 7.35 (2H, d, J=8.8 Hz), 7.51 (2H, d, J=8.8 Hz), 7.75 (1H, s), 7.90(1H, dd, J=4.8, 1.6 Hz), 9.41 (1H, s), 10.42 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.4 S:                              C            H      N                                             ______________________________________                                        Calculated: 58.21        4.61   11.31                                         Found:      58.21        4.74   11.01                                         ______________________________________                                    

Example 24

N-(2-Anilino-3-pyridyl)-4-chlorobenzenesulfonamide: ##STR56##

The title compound was produced in the same manner as that of Example 1.

Melting point: 186° to 188° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 360 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.77 (1H, dd, J=7.6, 4.8 Hz), 6.90 (1H, dt,J=7.6, 0.8 Hz), 7.22 (2H, t, J=7.6 Hz), 7.30 (1H, dd, J=7.6, 1.2 Hz),7.38 (2H, dd, J=7.6, 0.8 Hz), 7.51 (2H, d, J=8.4 Hz), 7.64 (2H, d, J=8.4Hz), 7.89 (1H, s), 8.02 (1H, dd, J=4.8, 1.2 Hz), 9.76 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.14 C1N.sub.3 O.sub.2 S:                            C            H      N                                             ______________________________________                                        Calculated: 56.74        3.92   11.68                                         Found:      56.79        4.03   11.67                                         ______________________________________                                    

Example 25

N-(2-Anilino-3-pyridyl)-3-chlorobenzenesulfonamide: ##STR57##

The title compound was produced in the same manner as that of Example 1.

Melting point: 143° to 144° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 360 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.77 (1H, dd, J=7.6, 4.8 Hz), 6.91 (1H, dt,J=7.6, 1.2 Hz), 7.21 (2H, t, J=7.6 Hz), 7.32 (1H, dd, J=7.6, 1.6 Hz),7.41 (2H, dd, J=7.6, 1.2 Hz), 7.46 (1H, t, J=8.0 Hz), 7.54-7.61 (2H, m),7.68 (1H, br-s), 7.92 (1H, br-s), 8.04 (1H, dd, J=4.8, 1.6 Hz), 9.80(1H, br-s)

    ______________________________________                                        Elementary anlysis for C.sub.17 H.sub.14 C1N.sub.3 O.sub.2 S:                             C            H      N                                             ______________________________________                                        Calculated: 56.74        3.92   11.68                                         Found:      56.73        4.09   11.68                                         ______________________________________                                    

Example 26

N-(2-Anilino-3-pyridyl)-3-methylbenzenesulfonamide: ##STR58##

The title compound was produced in the same manner as that of Example 1.

Melting point: 161° to 162° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 340 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.22 (3H, s), 6.74 (1H, dd, J=7.6, 4.8 Hz),6.90 (1H, dt, J=7.2, 1.2 Hz), 7.21 (2H, t, J=7.2 Hz), 7.27-7.35 (3H, m),7.42 (2H, dd, J=7.2, 1.2 Hz), 7.45 (1H, td, J=7.2, 2.0 Hz), 7.52 (1H,br-s), 7.92 (1H, s), 8.00 (1H, dd, J=4.8, 1.2 Hz), 9.68 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 63.70        5.05   12.38                                         Found:      63.81        5.16   12.43                                         ______________________________________                                    

Example 27

N-(2-Anilino-3-pyridyl)-4-ethoxybenzenesulfonamide: ##STR59##

The title compound was produced in the same manner as that of Example 1.

Melting point: 161° to 162° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.26 (3H, t, J=7.0 Hz), 3.94 (2H, q, J=7.0Hz), 6.74 (1H, dd, J=7.6, 4.8 Hz), 6.89 (1H, tt, J=7.2, 0.8 Hz), 6.92(2H, d, J=8.8 Hz), 7.21 (2H, t, J=7.2 Hz), 7.27 (1H, dd, J=7.6, 1.6 Hz),7.42 (2H, dd, J=7.2, 0.8 Hz), 7.57 (2H, d, J=8.8 Hz), 7.88 (1H, s), 7.99(1H, dd, J=4.8, 1.6 Hz), 9.53 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 61.77        5.18   11.37                                         Found:      61.72        5.31   11.43                                         ______________________________________                                    

Example 28

4-Acetylamino-N-(2-anilino-3-pyridyl)benzenesulfonamide: ##STR60##

The title compound was produced in the same manner as that of Example 1.

Melting point: 234° to 236° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 383 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.04 (3H, s), 6.72 (1H, dd, J=7.6, 4.8 Hz),6.90 (1H, tt, J=8.0, 1.2 Hz), 7.19-7.24 (3H, m), 7.45 (2H, dd, J=8.0,1.2 Hz), 7.60 (2H, d, J=9.2 Hz), 7.65 (2H, d, J=9.2 Hz), 7.91 (1H, s),7.98 (1H, dd, J=4.8, 1.6 Hz), 9.60 (1H, br-s), 10.23 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.18 N.sub.4 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 59.67        4.74   14.65                                         Found:      59.69        4.82   14.38                                         ______________________________________                                    

Example 29

N-(2-Anilino-3-pyridyl)-4-phenoxybenzenesulfonamide: ##STR61##

The title compound was produced in the same manner as that of Example 1.

Melting point: 164° to 166° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 418 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.78 (1H, dd, J=7.6, 4.8 Hz), 6.84 (2H, dd,J=7.6, 1.2 Hz), 6.91-6.96 (3H, m), 7.19-7.27 (3H, m), 7.36-7.40 (3H, m),7.44 (2H, dd, J=7.6, 1.2 Hz), 7.62 (2H, d, J=9.2 Hz), 7.85 (1H, s), 8.02(1H, dd, J=4.8, 1.6 Hz), 9.62 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.23 H.sub.19 N.sub.3 O.sub.3 S:                              C            H      N                                             ______________________________________                                        Calculated: 66.17        4.59   10.06                                         Found:      66.15        4.68   10.04                                         ______________________________________                                    

Example 30

N-(2-Anilino-3-pyridyl)-4-cyanobenzenesulfonamide: ##STR62##

The title compound was produced in the same manner as that of Example 1.

Melting point: 155° to 157° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 351 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.80 (1H, dd, J=7.6, 4.8 Hz), 6.90 (1H, t,J=7.6 Hz), 7.20 (2H, t, J=7.6 Hz), 7.31 (2H, d, J=7.6 Hz), 7.36 (1H, dd,J=7.6, 1.6 Hz), 7.76 (2H, d, J=7.6 Hz), 7.86-7.89 (3H, m), 8.05 (1H,br), 9.90 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.14 N.sub.4 O.sub.2 S:                              C            H      N                                             ______________________________________                                        Calculated: 61.70        4.03   15.99                                         Found:      61.73        4.14   15.75                                         ______________________________________                                    

Example 31

N-(2-Anilino-3-pyridyl)-2,4-dimethoxybenzenesulfonamide: ##STR63##

The title compound was produced in the same manner as that of Example 1.

Melting point: 176° to 178° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.76 (3H, s), 3.81 (3H, s), 6.53 (1H, dd,J=8.8, 2.4 Hz), 6.59 (1H, d, J=2.4 Hz), 6.69 (1H, dd, J=7.6, 4.8 Hz),6.92 (1H, t, J=7.6 Hz), 7.25 (2H, t, J=7.6 Hz), 7.33 (1H, dd, J=7.6, 1.6Hz), 7.50 (2H, d, J=7.6 Hz), 7.55 (1H, d, J=8.8 Hz), 7.92 (1H, dd,J=4.8, 1.6 Hz), 8.07 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.21         4.97   10.90                                         Found:     59.19         5.04   10.91                                         ______________________________________                                    

EXAMPLE 32

N-(2-Anilino-3-pyridyl)-2-chlorobenzenesulfonamide: ##STR64##

The title compound was produced in the same manner as that of Example 1.

Melting point: 140° to 141° C. (recrystallized from toluene)

FAB mass spectrometry m/z: 360 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 6.72 (1H, dd, J=7.6, 4.8 Hz), 6.93 (1H, t,J=7.6 Hz), 7.25 (2H, t, J=7.6 Hz), 7.31 (1H, dd, J=7.6, 1.6 Hz),7.42-7.46 (1H, m), 7.49 (2H, d, J=7.6 Hz), 7.56-7.59 (2H, m), 7.87 (1H,d, J=7.6 Hz), 7.95-8.01 (2H, m), 10.14 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.14 ClN.sub.3 O.sub.2 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              56.74         3.92   11.68                                         Found:     56.86         4.06   11.62                                         ______________________________________                                    

EXAMPLE 33

4-Acetyl-N-(2-anilino-3-pyridyl)benzenesulfonamide: ##STR65##

The title compound was produced in the same manner as that of Example 1.

Melting point: 171° to 173° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 368 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.46 (3H, s), 6.78 (1H, dd, J=7.6, 4.8 Hz),6.85 (1H, t, J=7.6 Hz), 7.15 (2H, t, J=7.6 Hz), 7.31 (2H, dd, J=7.6, 1.2Hz), 7.35 (1H, dd, J=7.6, 1.6 Hz), 7.74 (2H, d, J=8.4 Hz), 7.85 (1H, s),7.94 (2H, d, J=8.4 Hz), 8.03 (1H, dd, J=4.8, 1.6 Hz), 9.83 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 N.sub.3 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              62.11         4.66   11.44                                         Found:     62.31         4.78   11.19                                         ______________________________________                                    

EXAMPLE 34

N-[2-[(3-Hydroxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR66##

4.0 g (19.9 mmol) of the compound produced in Production Example 6 wasreacted with 4.11 g (19.9 mmol) of p-methoxybenzenesulfonyl chloride andthe product was treated in the same manner as that of Example 1 toobtain 5.0 g of the title compound.

Melting point: 181° to 182° C. (recrystallized from toluene)

FAB mass spectrometry m/z: 372 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.72 (3H, s), 6.31 (1H, dd, J=8.0, 2.0 Hz),6.72 (1H, dd, J=7.6, 4.8 Hz), 6.79 (1H, d, J=8.0 Hz), 6.96 (2H, d, J=8.8Hz), 6.98 (1H, t, J=8.0 Hz), 7.02 (1H, t, J=2.0 Hz), 7.25 (1H, dd,J=7.6, 1.6 Hz), 7.59 (2H, d, J=8.8 Hz), 7.77 (1H, s), 7.99 (1H, dd,J=4.8, 1.6 Hz), 9.18 (1H, s), 9.56 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.21         4.61   11.31                                         Found:     58.26         4.67   10.99                                         ______________________________________                                    

EXAMPLE 35

N[2-[(4-Ethoxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR67##

The title compound was produced in the same manner as that of Example 1.

Melting point: 144° to 146° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 400 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.31 (3H, t, J=2.8 Hz), 3.73 (3H, s), 3.97(2H, q, J=2.8 Hz), 6.65 (1H, dd, J=4.8, 7.6 Hz), 6.80 (2H, d, J=8.8 Hz),6.98 (2H, d, J=8.8 Hz), 7.21 (1H, dd, J=1.6, 7.6 Hz), 7.28 (2H, d, J=8.8Hz), 7.60 (2H, d, J=8.8 Hz), 7.72 (1H, br-s), 7.92 (1H, dd, J=1.6, 4.8Hz), 9.47 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.21 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.13         5.30   10.52                                         Found:     60.02         5.27   10.21                                         ______________________________________                                    

EXAMPLE 36

N-[2-[(4-hydroxy-3-methylphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR68##

The title compound was produced in the same manner as that of Example 1.

Melting point: 89° to 91° C. (recrystallized from toluene)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.07 (3H, s), 3.75 (3H, s), 6.60 (1H, dd,J=4.8, 7.6 Hz), 6.63 (1H, d, J=8.4 Hz), 6.93 (1H, d, J=2.8 Hz),6.98-7.03 (3H, m), 7.18 (1H, dd, J=1.6, 7.6 Hz), 7.50 (1H, br-s), 7.60(2H, d, J=8.8 Hz), 7.88 (1H, dd, J=1.6, 4.8 Hz), 8.87 (1H, s), 9.44 (1H,br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.21         4.97   10.90                                         Found:     58.97         5.06   10.53                                         ______________________________________                                    

EXAMPLE 37

Ethyl 4-[[3-(4-methoxybenzenesulfonamido)-2-pyridyl]amino]benzoate:##STR69##

The title compound was produced in the same manner as that of Example 1.

Melting point: 172° to 173° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 428 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.31 (3H, t, J=3.2 Hz), 3.63 (3H, s), 4.27(2H, q, J=3.2 Hz), 6.88 (2H, d, J=8.8 Hz), 6.88 (1H, dd, J=4.8, 7.6 Hz),7.38 (1H, dd, J=1.6, 7.6 Hz), 7.51 (2H, d, J=8.8 Hz), 7.54 (2H, d, J=8.8Hz), 7.80 (2H, d, J=8.8 Hz), 8.10 (1H, dd, J=1.6, 4.8 Hz), 8.34 (1H,br-s), 9.58 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.21 N.sub.3 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.00         4.95   9.83                                          Found:     58.98         4.91   9.63                                          ______________________________________                                    

Example 384-Methoxy-N-[2-[(4-methylthiophenyl)amino]-3-pyridyl]-benzenesulfonamide:##STR70##

The title compound was produced in the same manner as that of Example 1.

Melting point: 148° to 149° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 402 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.43 (3H, s), 3.70 (3H, s), 6.73 (1H, dd,J=4.8, 7.6 Hz), 6.94 (2H, d, J=8.8 Hz), 7.17 (2H, d, J=8.8 Hz), 7.26(1H, dd, J=1.6, 7.6 Hz), 7.39 (2H, d, J=8.8 Hz), 7.57 (2H, d, J=8.8 Hz),7.93 (1H, br-s), 7.98 (1H, dd, J=1.6, 4.8 Hz), 9.51 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S.sub.2 :                    C           H      N                                                 ______________________________________                                        Calculated:                                                                              56.84         4.77   10.47                                         Found:     56.90         4.77   10.24                                         ______________________________________                                    

Example 39

Potassium 4-[[3-(4-methoxybenzenesulfonamido)-2-pyridyl]amino]phenylsulfate: ##STR71##

2.0 g (5.38 mmol) of the compound of Example 6 was dissolved in 20 ml ofpyridine. 800 mg (6.87 mmol) of chlorosulfonic acid (95%) was addeddropwise thereto at -15° to -10° C. The temperature was slowly elevatedto room temperature and the mixture was stirred for 3 days. A 1N aqueouspotassium carbonate solution was added to the reaction mixture to adjustthe pH to 8 to 9. The solvent was distilled off under reduced pressure.Water and ethyl acetate were added to the residue and an aqueous layerthus formed was separated, concentrated, purified by silica gel columnchromatography and precipitated with methanol/dichloromethane to obtain1.58 g of the title compound.

Melting point: 165° to 166° C.

FAB mass spectrometry m/z: 528 ([M+K]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.73 (3H, s), 6.68 (1H, dd, J=4.8, 8.0 Hz),6.98 (2H, d, J=8.8 Hz), 7.02 (2H, d, J=8.4 Hz), 7.25-7.27 (3H, m), 7.61(2H, d, J=8.8 Hz), 7.83 (1H, s), 7.94 (1H, dd, J=1.2, 4.8 Hz), 9.55 (1H,s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 N.sub.3 O.sub.7 S.sub.2             K.3/2H.sub.2 O:                                                                        C           H      N                                                 ______________________________________                                        Calculated:                                                                              41.85         3.71   8.13                                          Found:     41.88         3.41   8.08                                          ______________________________________                                    

Example 40

4-Methoxy-N-[2-[(4-phenoxyphenyl)amino]-3-pyridyl]-benzenesulfonamide:##STR72##

The title compound was produced in the same manner as that of Example 1.

Melting point: 174° to 176° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 448 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.72 (1H, dd, J=4.8, 7.6 Hz),6.92 (2H, d, J=8.8 Hz), 6.91-6.97 (2H, m), 6.96 (2H, d, J=8.8 Hz),7.05-7.10 (1H, m), 7.27 (1H, dd, J=1.6, 7.6 Hz), 7.32-7.40 (2H, m), 7.43(2H, d, J=8.8 Hz), 7.59 (2H, d, J=8.8 Hz), 7.92 (1H, br-s), 7.98 (1H,dd, J=1.6, 4.8 Hz), 9.44 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.24 H.sub.21 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              64.41         4.73   9.39                                          Found:     64.71         4.96   9.30                                          ______________________________________                                    

Example 41

4-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]benzoic acid:##STR73##

The title compound was produced by an alkaline hydrolysis of thecompound of Example 37 in an ordinary manner.

Melting point: 248° to 250° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 400 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.64 (3H, s), 6.87 (1H, dd, J=4.8, 7.6 Hz),6.89 (2H, d, J=8.8 Hz), 7.37 (1H, dd, J=1.6, 7.6 Hz), 7.49 (2H, d, J=8.8Hz), 7.54 (2H, d, J=8.8 Hz), 7.78 (2H, d, J=8.8 HZ), 8.09 (1H, dd,J=1.6, 4.8 Hz), 8.29 (1H, br-s), 9.58 (1H, br-s), 12.44 (1H, br)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 N.sub.3 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              57.13         4.29   10.52                                         Found:     57.10         4.42   10.35                                         ______________________________________                                    

Example 42

N-[2-[(4-Chlorophenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR74##

The title compound was produced in the same manner as that of Example 1.

Melting point: 205° to 207° C. (decomp.) (recrystallized from ethanol)

FAB mass spectrometry m/z: 390 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.70 (3H, s), 6.78 (1H, dd, J=7.6, 4.8 Hz),6.93 (2H, d, J=8.8 Hz), 7.24 (2H, d, J=8.8 Hz), 7.30 (1H, dd, J=7.6, 2.0Hz), 7.45 (2H, d, J=8.8 Hz), 7.56 (2H, d, J=8.8 Hz), 8.02 (1H, dd,J=4.8, 2.0 Hz), 8.05 (1H, s), 9.51 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 ClN.sub.3 O.sub.3 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.46         4.14   10.78                                         Found:     55.44         4.32   10.71                                         ______________________________________                                    

Example 43

N-[2-[(2-Hydroxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR75##

The title compound was produced in the same manner as that of Example 1.

Melting point: 154° to 155° C. (recrystallized from toluene)

FAB mass spectrometry m/z: 372 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.81 (3H, s), 6.63 (1H, dd, J=8.0, 5.2 Hz),6.72-6.79 (2H, m), 6.82-6.86 (2H, m), 7.07 (2H, d, J=8.8 Hz), 7.66 (2H,d, J=8.8 Hz), 8.05 (1H, dd, J=5.2, 1.6 Hz), 8.15 (1H, s), 8.29 (1H, dd,J=7.6, 2.0 Hz), 9.70 (1H, s), 9.94 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.22         4.61   11.32                                         Found:     58.39         4.60   11.20                                         ______________________________________                                    

Example 44

N-(2-Anilino-3-pyridyl)-2,4,6-trimethylbenzenesulfonamide: ##STR76##

The title compound was produced in the same manner as that of Example 1.

Melting point: 140° to 142° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 368 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.16 (3H, s), 2.41 (6H, s), 6.70 (1H, dd,J=7.6, 4.8 Hz), 6.89-6.94 (3H, m), 7.08 (1H, dd, J=7.6, 1.6 Hz), 7.24(2H, t, J=7.6 Hz), 7.43 (2H, d, J=7.6 Hz), 7.89 (1H, s), 8.01 (1H, dd,J=4.8, 1.6 Hz), 9.58 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.21 N.sub.3 O.sub.2 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              65.37         5.76   11.43                                         Found:     65.45         5.67   11.34                                         ______________________________________                                    

Example 45

N-(2-Anilino-3-pyridyl)-4-chloro-2,5-dimethylbenzenesulfonamide:##STR77##

The title compound was produced in the same manner as that of Example 1.

Melting point: 153° to 154° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 388 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.20 (3H, s), 2.41 (3H, s), 6.75 (1H, dd,J=7.6, 4.8 Hz), 6.91 (1H, t, J=7.6 Hz), 7.23 (2H, t, J=7.6 Hz), 7.26(1H, dd, J=7.6, 1.6 Hz), 7.33 (1H, s), 7.38 (2H, d, J=7.6 Hz), 7.63 (1H,s), 7.93 (1H, s), 8.02 (1H, dd, J=4.8, 1.6 Hz), 9.76 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.18 ClN.sub.3 O.sub.2 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.83         4.68   10.83                                         Found:     58.97         4.64   10.85                                         ______________________________________                                    

Example 46

4-Methoxy-N-[2-[(2-methoxy-5-pyridyl)amino]-3-pyridyl]benzenesulfonamide:##STR78##

The title compound was produced in the same manner as that of Example 1.

Melting point: 159° to 160° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 387 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.73 (3H, s), 3.81 (3H, s), 6.68-6.73 (2H,m), 6.98 (2H, d, J=8.8 Hz), 7.25 (1H, dd, J=7.6, 1.2 Hz), 7.60 (2H, d,J=8.8 Hz), 7.72 (1H, dd, J=8.8, 2.8 Hz), 7.90 (1H, s), 7.93 (1H, dd,J=4.8, 1.2 Hz), 8.13 (1H, d, J=2.8 Hz), 9.44 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.18 N.sub.4 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.95         4.69   14.50                                         Found:     55.95         4.72   14.46                                         ______________________________________                                    

Example 47

N-(4-Anilino-6-methoxy-5-pyrimidyl)-4-methoxybenzenesulfonamide:##STR79##

The title compound was produced in the same manner as that of Example 1.

Melting point: 159° to 160° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 387 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.38 (3H, s), 3.80 (3H, s), 7.01-7.07 (3H,m), 7.30 (2H, t, J=8.0 Hz), 7.57 (2H, dd, J=8.0, 0.8 Hz), 7.63 (2H, d,J=8.8 Hz), 8.20 (1H, s), 8.33 (1H, s), 9.29 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.18 N.sub.4 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.95         4.70   14.50                                         Found:     55.90         4.71   14.49                                         ______________________________________                                    

Example 48

N-(4-Anilino-6-chloro-5-pyrimidyl)-4-methoxybenzenesulfonamide:##STR80##

The title compound was produced in the same manner as that of Example 1.

Melting point: 174° to 175° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 391 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 7.03 (2H, d, J=8.8 Hz), 7.09(1H, t, J=7.6 Hz), 7.32 (2H, t, J=7.6 Hz), 7.46 (2H, d, J=7.6 Hz), 7.65(2H, d, J=8.8 Hz), 8.29 (1H, s), 8.63 (1H, s), 9.74 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.15 N.sub.4 O.sub.3 SCl:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              52.24         3.87   14.33                                         Found:     52.29         3.85   14.27                                         ______________________________________                                    

Example 49

N-(2-Anilino-6-dimethylamino-3-pyridyl)-4-methoxybenzenesulfonamide:##STR81##

The title compound was produced in the same manner as that of Example 1.

Melting point: 152° to 153° C. (recrystallized from ethylacetate/n-hexane):

FAB mass spectrometry m/z: 399 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 3.04 (6H, s), 3.83 (3H, s), 5.71 (1H, d, J=8.8Hz), 5.75 (1H, s), 6.59 (1H, d, J=8.8 Hz), 6.91-6.96 (3H, m), 7.24-7.28(3H, m), 7.53 (2H, d, J=7.6 Hz), 7.72 (2H, d, J=9.2 Hz)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.22 N.sub.4 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.28         5.56   14.06                                         Found:     60.21         5.47   13.92                                         ______________________________________                                    

Example 50

N-(2-Anilino-6-chloro-3-pyridyl)-4-methoxybenzenesulfonamide: ##STR82##

The title compound was produced in the same manner as that of Example 1.

Melting point: 206° to 208° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 390 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 6.79 (1H, d, J=8.0 Hz),6.93-6.99 (3H, m), 7.26 (3H, t, J=8.0 Hz), 7.38 (2H, d, J=8.0 Hz), 7.61(2H, d, J=9.2 Hz), 8.15 (1H, s), 9.56 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 ClN.sub.3 O.sub.3 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.46         4.14   10.78                                         Found:     55.49         4.04   10.62                                         ______________________________________                                    

Example 51

N-(4-Anilino-3-pyridyl)-4-methoxybenzenesulfonamide: ##STR83##

The title compound was produced in the same manner as that of Example 1.

Melting point: 201° to 202° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 356 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.92 (1H, d, J=6.4 Hz), 6.95(2H, d, J=8.8 Hz), 7.13-7.20 (3H, m), 7.39 (2H, t, J=8.0 Hz), 7.67 (2H,d, J=8.8 Hz), 7.78 (1H, s), 7.82 (1H, d, J=5.6 Hz)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.83         4.82   11.82                                         Found:     60.78         4.77   11.84                                         ______________________________________                                    

Example 52

N-[2-[(4-Dimethylcarbamoyloxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR84##

The title compound was produced in the same manner as that of Example 1.

Melting point: 202° to 203° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 443 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.90 (3H, s), 3.03 (3H, s), 3.72 (3H, s),6.72 (1H, dd, J=7.6, 4.8 Hz), 6.96 (2H, d, J=8.8Hz), 6.97 (2H, d, J=8.8Hz), 7.26 (1H, dd, J=7.6, 1.6 Hz), 7.41 (2H, d, J=8.8 Hz), 7.60 (2H, d,J=8.8 Hz), 7.94 (1H, s), 7.97 (1H, dd, J=4.8, 1.6 Hz), 9.52 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.22 N.sub.4 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              57.00         5.01   12.66                                         Found:     57.35         4.98   12.55                                         ______________________________________                                    

Example 53

N-(4-Anilino-5-pyrimidyl)-4-methoxybenzenesulfonamide: ##STR85##

The title compound was produced by catalytically reducing the compoundof Example 48 in the presence of palladium/carbon in an ordinary manner.

Melting point: 189° to 190° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 357 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.73 (3H, s), 7.01 (2H, d, J=8.8 Hz), 7.05(1H, t, J=8.0 Hz), 7.30 (2H, t, J=8.0 Hz), 7.50 (2H, d, J=8.0 Hz), 7.64(2H, d, J=8.8 Hz), 7.87 (1H, s), 8.40 (1H, s), 8.57 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.16 N.sub.4 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              57.29         4.53   15.72                                         Found:     57.25         4.68   15.36                                         ______________________________________                                    

Example 54

N-(2-Anilino-6-methoxy-3-pyridyl)-4-methoxybenzenesulfonamide: ##STR86##

The title compound was produced in the same manner as that of Example 1.

Melting point: 187° to 188° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.70 (3H, s), 3.77 (3H, s), 6.11 (1H, d,J=8.0 Hz), 6.89 (1H, t, J=7.6 Hz), 6.95 (2H, d, J=9.2 Hz), 7.07 (1H, d,J=8.0 Hz), 7.22 (2H, t, J=7.6 Hz), 7.43 (2H, d, J=7.6 Hz), 7.52 (2H, d,J=9.2 Hz), 7.83 (1H, br-s), 9.23 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.21         4.97   10.90                                         Found:     59.32         4.97   10.76                                         ______________________________________                                    

Example 55

N-(4,6-Dianilino-5-pyrimidyl)-4-methoxybenzenesulfonamide: ##STR87##

The title compound was produced in the same manner as that of Example 1.

Melting point: 149° to 151° C. (recrystallized fromdichloromethane/n-hexane)

FAB mass spectrometry m/z: 448 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.53 (3H, s), 6.82 (2H, d, J=8.8 Hz), 6.96(2H, t, J=7.6 Hz), 7.23 (4H, t, J=7.6 Hz), 7.40 (4H, d, J=7.6 Hz), 7.62(2H, d, J=8.8 Hz), 8.05 (2H, s), 8.11 (1H, s), 8.90 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.23 H.sub.21 N.sub.5 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.73         4.73   15.65                                         Found:     61.91         4.72   15.74                                         ______________________________________                                    

Example 56

4-Methoxy-N-[2-(methylphenyl)amino-3-pyridyl]benzenesulfonamide:##STR88##

The title compound was produced in the same manner as that of Example 1.

Melting point: 80° to 81° C. (recrystallized from diisopropyl ether)

FAB mass spectrometry m/z: 370 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.01 (3H, s), 3.82 (3H, s), 6.46-6.51 (2H,m), 6.78-6.84 (1H, m), 7.04 (2H, d, J=8.8 Hz), 7.11-7.17 (2H, m), 7.17(1H, dd, J=4.8, 8.0 Hz), 7.65 (1H, dd, J=1.6, 8.0 Hz), 7.68 (2H, d,J=8.8 Hz), 8.14 (1H, dd, J=1.6, 4.8 Hz), 9.30 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.77         5.18   11.38                                         Found:     61.85         5.28   11.36                                         ______________________________________                                    

Example 57

4-Methoxy-N-[2-[(2-pyrimidyl)amino]phenyl]benzenesulfonamide: ##STR89##

The title compound was produced in the same manner as that of Example 1.

Melting point: 193° to 195° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 357 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.70 (3H, s), 6.79-6.83 (3H, m), 6.96 (1H,dt, J=1.6, 8.4 Hz), 7.01 (1H, dd, J=1.6, 8.4 Hz), 7.19 (1H, dt, J=1.6,8.4 Hz), 7.47 (2H, d, J=8.8 Hz), 7.87 (1H, dd, J=1.6, 8.4 Hz), 8.38 (2H,dd, J=1.6, 4.8 Hz), 8.54 (1H, br-s), 9.53 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.17 H.sub.16 N.sub.4 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              57.29         4.53   15.72                                         Found:     57.18         4.57   15.80                                         ______________________________________                                    

Example 58

N-(2-Anilinophenyl)-4-methoxybenzenesulfonamide: ##STR90##

The title compound was produced in the same manner as that of Example 1.

Melting point: 140° to 142° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 354 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.69 (3H, s), 6.66-6.72 (2H, m), 6.81 (2H, d,J=8.8 Hz), 6.76-6.87 (2H, m), 7.04-7.17 (5H, m), 7.24 (1H, br-s), 7.52(2H, d, J=8.8 Hz), 9.30 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.18 N.sub.2 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              64.39         5.12   7.90                                          Found:     64.49         5.17   7.77                                          ______________________________________                                    

Example 59

N-[2-[(4-Benzoyloxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR91##

The title compound was produced in the same manner as that of Example 1.

Melting point: 208° to 210° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 476 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.73 (3H, s), 6.75 (1H, d, J=4.8, 7.6 Hz),6.98 (2H, d, J=8.8 Hz), 7.13 (2H, d, J=8.8 Hz), 7.28 (1H, dd, J=1.6, 7.6Hz), 7.51 (2H, d, J=8.8 Hz), 7.61 (2H, d, J=8.8 Hz), 7.58-7.65 (2H, m),7.72-7.78 (1H, m), 8.00 (1H, dd, J=1.6, 4.8 Hz), 8.04 (1H, br-s),8.11-8.16 (2H,m), 9.54 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.25 H.sub.21 N.sub.3 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              63.15         4.45   8.84                                          Found:     62.95         4.57   8.76                                          ______________________________________                                    

Example 60

N-[2-[[4-(tert-Butoxycarbonylaminoacetyloxy)phenyl]amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR92##

The title compound was produced in the same manner as that of Example 1.

¹ H-NMR (CDCl₃) δ (ppm): 1.47 (9H, s), 3.82 (3H, s), 4.18 (2H, d, J=5.6Hz), 5.17 (1H, br-s), 6.58 (2H, dd, J=7.6, 4.8 Hz), 6.89 (1H, dd, J=7.6,1.6 Hz), 6.90 (2H, d, J=8.8 Hz), 7.00 (2H, d, J=8.8 Hz), 7.35 (1H,br-s), 7.47 (2H, d, J=8.8 Hz), 7.68 (2H, d, J=8.8 Hz), 8.10 (1H, dd,J=4.8, 1.6 Hz)

Example 61

N-[2-[[4-(Aminoacetyloxy)phenyl]amino]-3-pyridyl]-4-methoxybenzenesulfonamidedihydrochloride: ##STR93##

272 mg (0.515 mmol) of the compound of Example 60 was added to 10 ml oftetrahydrofuran. 2 ml of concentrated hydrochloric acid was added to themixture and stirred at room temperature for 3 h. The solvent wasdistilled off under reduced pressure and the residue was recrystallizedfrom ethanol to obtain 159 mg of the title compound.

Melting point: 196° to 199° C. (decomp.)

FAB mass spectrometry m/z: 429 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 4.08-4.11 (2H, m), 6.78 (1H,dd, J=4.8, 7.6 Hz), 6.94 (2H, d, J=8.8 Hz), 7.04 (2H, d, J=8.8 Hz), 7.32(1H, dd, J=1.6, 7.6 Hz), 7.48-7.51 (2H, m), 7.61 (2H, d, J=8.8 Hz), 7.97(1H, dd, J=1.6, 4.8 Hz), 8.48 (3H, br-s), 9.84 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.20 N.sub.4 O.sub.5 S.2HCl.1/2H.sub.    2 O:                                                                                   C           H      N                                                 ______________________________________                                        Calculated:                                                                              47.07         4.54   10.98                                         Found:     47.38         4.45   10.78                                         ______________________________________                                    

Example 62

4-Methoxy-N-[2-[(4-methoxyphenyl)amino]-3-pyridyl]-N-methylbenzenesulfonamide:##STR94##

500 mg (1.3 mmol) of the compound of Example 4 was dissolved in 5 ml ofdimethylformamide. 60 mg (1.5 mmol) of sodium hydride (60%) was added tothe solution. The resulting solution was stirred at room temperature for30 min and 95 μl (1.5 mmol) of methyl iodide was added thereto.

After stirring overnight, the solvent was distilled off under reducedpressure. The resultant residue was dissolved in ethyl acetate and thesolution was washed with water. After drying over magnesium sulfate, itwas concentrated and purified by silica gel column chromatography toobtain 290 mg of the title compound.

FAB mass spectrometry m/z: 400 ([M+H]⁺)

¹ H-NMR (CDCl₃) δ (ppm): 3.15 (3H, s), 3.80 (3H, s), 3.88 (3H, s), 6.50(1H, dd, J=4.8, 7.6 Hz), 6.67 (1H, dd, J=1.6, 7.6 Hz), 6.89 (2H, d,J=8.8 Hz), 6.98 (2H, d, J=8.8 Hz), 7.29 (1H, br-s), 7.47 (2H, d, J=8.8Hz), 7.65 (2H, d, J=8.8 Hz), 8.09 (1H, dd, J=1.6, 4.8 Hz)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.21 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.14         5.30   10.52                                         Found:     60.08         5.39   10.29                                         ______________________________________                                    

Example 63

N-[2-[[4-(2-Aminobenzoyloxy)phenyl]amino]-3-pyridyl]-4-methoxybenzenesulfonamide:##STR95##

500 mg (1.35 mmol) of the compound of Example 6, 260 mg (1.59 mmol) ofisatoic anhydride and 170 mg (1.39 mmol) of 4-dimethylaminopyridine weredissolved in 5 ml of dimethylformamide and the solution was stirred at80° C. for 5 h. The solvent was distilled off under reduced pressure andethyl acetate was added to the residue. A precipitate thus formed wasrecrystallized from ethanol to obtain 500 mg of the title compound.

Melting point: 221° to 225° C. (decomp.)

FAB mass spectrometry m/z: 491 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.74 (3H, s), 6.60 (1H, td, J=1.6, 8.4 Hz),6.73 (2H, br-s), 6.74 (1H, dd, J=4.8, 8.0 Hz), 6.83 (1H, dd, J=0.8, 8.4Hz), 6.98 (2H, d, J=8.8 Hz), 7.08 (2H, d, J=9.2 Hz), 7.27 (1H, dd,J=2.0, 8.0 Hz), 7.33 (1H, td, J=1.6, 7.2 Hz), 7.49 (1H, d, J=9.2 Hz),7.61 (2H, d, J=8.8 Hz), 7.92 (1H, dd, J=1.6, 8.4 Hz), 7.99 (1H, dd,J=2.0, 4.8 Hz), 8.02 (1H, s), 9.60 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.25 H.sub.22 N.sub.4 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.21         4.52   11.42                                         Found:     60.98         4.52   11.24                                         ______________________________________                                    

Example 64

4-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]phenyldihydrogenphosphate: ##STR96##

7.44 g (20 mmol) of the compound of Example 6 was suspended in 100 ml ofphosphorus oxychloride and the suspension was heated under reflux untila homogeneous solution was obtained. Phosphorus oxychloride wasdistilled off under reduced pressure and then diisopropyl ether wasadded to the residue to form a solid, which was separated by filtrationand suspended in 100 ml of tetrahydrofuran. 50 ml of water was added tothe suspension under cooling with ice and stirred until a homogeneoussolution was obtained. After the solvent was distilled off under reducedpressure, 100 ml of methanol and 100 ml of water were added to theresidue to obtain a solution, which was concentrated under reducedpressure until an insoluble matter was formed. The insoluble matter wasremoved and the residue was further concentrated under reduced pressureand the resultant precipitate was separated by filtration to obtain 4.27g of the title compound.

Melting point: 215° to 216° C.

FAB mass spectrometry m/z: 452 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.73 (3H, s), 6.70 (1H, dd, J=7.6, 4.8 Hz),6.98 (2H, d, J=8.8 Hz), 7.02 (2H, d, J=8.8 Hz), 7.24 (1H, dd, J=7.6, 1.6Hz), 7.35 (2H, d, J=8.8 Hz), 7.60 (2H, d, J=8.8 Hz), 7.88 (1H, s), 7.95(1H, dd, J=4.8, 1.6 Hz), 9.50 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.18 N.sub.3 O.sub.7 PS:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              47.90         4.02   9.31                                          Found:     47.72         4.00   9.39                                          ______________________________________                                    

Example 65

3-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]phenyldihydrogenphosphate: ##STR97##

120 mg of the title compound was produced by reacting 1.00 g (2.7 mmol)of the compound of Example 34 with 10 ml of phosphorus oxychloride andthe product was treated in the same manner as that of Example 64.

Melting point: 166° to 168° C.

FAB mass spectrometry m/z: 452 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.70 (3H, s), 6.73 (1H, d, J=7.6 Hz), 6.77(1H, dd, J=7.6, 4.8 Hz), 6.95 (2H, d, J=8.8 Hz), 7.15 (1H, t, J=7.6 Hz),7.21 (1H, d, J=7.6 Hz), 7.30 (1H, dd, J=7.6, 1.6 Hz), 7.37 (1H, s), 7.59(2H, d, J=8.8 Hz), 8.01 (1H, dd, J=4.8, 1.6 Hz), 8.10 (1H, s), 9.61 (1H,br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.18 N.sub.3 O.sub.7 PS.H.sub.2 O:                C           H      N                                                 ______________________________________                                        Calculated:                                                                              46.06         4.29   8.95                                          Found:     46.16         4.13   8.83                                          ______________________________________                                    

Example 664-Methoxy-N-[2-[[4-(4-methoxybenzenesulfonyloxy)phenyl]amino]-3-pyridyl]benzenesulfonamide:##STR98##

The compound produced in Production Example 4 was reacted with4-methoxybenzenesulfonyl chloride in an equivalent ratio of 1:2 toobtain the title compound.

Melting point: 122° to 123° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 542 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 3.88 (3H, s), 6.76 (1H, dd,J=7.6, 4.8 Hz), 6.84 (2H, d, J=8.8 Hz), 6.94 (2H, d, J=8.8 Hz), 7.17(2H, d, J=8.8 Hz), 7.25 (1H, dd, J=7.6, 1.2 Hz), 7.42 (2H, d, J=8.8 Hz),7.56 (2H, d, J=8.8 Hz), 7.76 (2H, d, J=8.8 Hz), 7.98 (1H, dd, J=4.8, 1.2Hz), 8.06 (1H, s), 9.51 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.23 H.sub.23 N.sub.3 O.sub.7 S.sub.2 :                    C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.40         4.28   7.76                                          Found:     55.57         4.26   7.61                                          ______________________________________                                    

Example 67

N-[2-[(4-Hydroxyphenyl)amino]phenyl]-4-methoxybenzenesulfonamide:##STR99##

The title compound was produced in the same manner as that of Example 1.

Melting point: 163° to 164° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.76 (3H, s), 6.58-6.67 (5H, m), 6.77 (1H,br-s), 6.80 (1H, dd, J=1.6, 8.0 Hz), 6.90-7.00 (4H, m), 7.56 (2H, d,J=8.8 Hz), 9.05 (1H, s), 9.23 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.18 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.61         4.90   7.56                                          Found:     61.86         4.90   7.39                                          ______________________________________                                    

Example 68

4-Methoxy-N-[2-[(4-pivaloyloxyphenyl)amino]-3-pyridyl]-benzenesulfonamide:##STR100##

The title compound was produced in the same manner as that of Example 1.

Melting point: 188° to 189° C. (recrystallized from toluene)

FAB mass spectrometry m/z: 456 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.30 (9H, s), 3.72 (3H, s), 6.73 (1H, dd,J=7.6, 4.8 Hz), 6.94 (2H, d, J=8.8 Hz), 6.97 (2H, d, J=8.8 Hz), 7.25(1H, dd, J=7.6, 1.6 Hz), 7.45 (2H, d, J=8.8 Hz), 7.60 (2H, d, J=8.8 Hz),7.97-8.00 (2H, m), 9.52 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.23 H.sub.25 N.sub.3 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.64         5.53   9.22                                          Found:     60.57         5.43   8.95                                          ______________________________________                                    

Example 69

4-Methoxy-N-[2-[(4-pyridyl)amino]phenyl]benzenesulfonamide: ##STR101##

The title compound was produced in the same manner as that of Example 1.

Melting point: 185° to 187° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 356 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.67 (3H, s), 6.45 (2H, d, J=6.0 Hz), 6.73(2H, d, J=8.8 Hz), 7.07 (1H, dt, J=7.6, 1.2 Hz), 7.16 (1H, dt, J=7.6,1.2 Hz), 7.22 (1H, dd, J=7.6, 1.2 Hz), 7.28 (1H, dd, J=7.6, 1.2 Hz),7.45 (2H, d, J=8.8 Hz), 7.90 (1H, br-s), 8.05 (2H, d, J=6.0 Hz)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.83         4.82   11.82                                         Found:     61.08         4.86   11.87                                         ______________________________________                                    

Example 70

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-methylnicotinamide:##STR102##

0.97 g (7 mmol) of 2-methylnicotinic acid was suspended in 4.5 ml ofdichloromethane. 1.33 g (16.8 mmol) of pyridine and then 1.05 g (8.4mmol) of thionyl chloride were added to the solution. The mixture wasstirred at room temperature for 30 min and then a solution of 1.77 g(6.36 mmol) of the compound produced in Production Example 12 in 7 ml ofdichloromethane was added thereto. After stirring overnight, an aqueoussodium hydrogencarbonate solution was added thereto and the product wasextracted with dichloromethane. After concentration, ethanol was addedto the concentrate and crystals thus formed were separated by filtrationand recrystallized from ethanol to obtain 0.80 g of the title compound.

Melting point: 148° to 149° C.

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.56 (3H, s), 3.80 (3H, s), 7.02 (2H, d,J=8.8 Hz), 7.08 (1H, dd, J=2.0, 8.4 Hz), 7.11 (1H, dt, J=1.6, 4.4 Hz),7.18-7.27 (1H, m), 7.37 (1H, dd, J=4.8, 7.6 Hz), 7.57 (2H, d, J=8.8 Hz),7.71-7.84 (2H, m), 8.58 (1H, dd, J=1.6, 4.8 Hz), 9.37 (1H, br-s), 9.60(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.37         4.90   10.41                                         ______________________________________                                    

Example 71

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-4-methylnicotinamide:##STR103##

The title compound was produced in the same manner as that of Example70.

Melting point: 199° to 200° C. (recrystallized from methanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.58 (39, s), 3.81 (3H, s), 7.00-7.07 (3H,m), 7.09-7.18 (1H, m), 7.19-7.27 (1H, m), 7.62 (2H, d, J=8.4 Hz),7.74-7.80 (1H, m), 7.82 (1H, d, J=5.6 Hz), 8.80 (1H, d, J=5.6 Hz), 8.87(1H, s), 9.62 (1H, br-s), 10.16 (1H, br-s)

Example 72

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-3-methylisonicotinamide:##STR104##

The title compound was produced in the same manner as that of Example70.

Melting point: 194° to 195° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.36 (3H, s), 3.81 (3H, s), 7.03 (2H, d,J=8.8 Hz), 7.07 (1H, dd, J=1.6, 8.0 Hz), 7.12 (1H, dt, J=1.6, 8.0 Hz),7.20-7.27 (1H, m), 7.36 (1H, d, J=4.8 Hz), 7.58 (2H, d, J=8.8 Hz),7.76-7.83 (1H, m), 8.55-8.61 (2H, m), 9.39 (1H, br-s), 9.65 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.29         4.83   10.49                                         ______________________________________                                    

Example 73

4-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]phenylβ-D-glucopyranoside: ##STR105##

637 mg (0.908 mmol) of the compound produced in Production Example 11was dissolved in a mixture of 7 ml of 1N sodium hydroxide and 20 ml ofethanol and the solution was refluxed for 3 h. After cooling, 4 ml of 1Nhydrochloric acid was added to the solution and the mixture wasconcentrated. Ethyl acetate and water were added to the concentrate andthe ethyl acetate layer thus formed was separated, dried, concentratedand purified by silica gel column chromatography to obtain 270 mg of thetitle compound.

¹ H-NMR (DMSO-d₆ +D₂ O) δ (ppm): 3.15-3.33 (4H, m), 3.49 (1H, dd, J=5.6,11.6 Hz), 3.70-3.73 (4H, s+dd), 4.75 (1H, d, J=7.6 Hz), 6.68 (1H, dd,J=4.8, 8.0 Hz), 6.93 (2H, d, J=9.2 Hz), 6.97 (2H, d, J=9.2 Hz), 7.23(1H, dd, J=2.0, 7.6 Hz), 7.29 (2H, d, J=9.2 Hz), 7.60 (2H, d, J=9.2 Hz),7.95 (1H, dd, J=2.0, 4.8 Hz)

Example 74

4-[[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]amino]phenylβ-D-glucopyranoside uronate: ##STR106##

The title compound was produced in the same manner as that of ProductionExample 11 and Example 73.

¹ H-NMR (DMSO-D₆ +D₂ O) δ (ppm): 3.27 (1H, t, J=8.8 Hz), 3.33 (1H, t,J=8.8 Hz), 3.42 (1H, t, J=8.8 Hz), 3.71 (3H, s), 3.86 (1H, d, J=9.6 Hz),4.92 (1H, d, J=7.6 (Hz), 6.70 (1H, dd, J=5.2, 7.6 Hz) 6.90 (2H, d, J=8.8Hz), 6.96 (2H, d, J=8.8 Hz), 7.25 (1H, dd, J=1.6, 7.6 Hz), 7.29 (2H, d,J=8.8 Hz), 7.59 (2H, d, J=8.8 Hz), 7.95 (1H, dd, J=1.6, 5.2 Hz)

Example 75

4-Methoxy-N-[2-[(3,4,5-trimethoxyphenyl)amino]-3-pyridyl]benzenesulfonamide##STR107##

The title compound was produced in the same manner as that of Example 1.

FAB mass spectrometry m/z: 445 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.61 (3H, s), 3.71 (3H, s), 3.74 (6H, s),6.72 (1H, dd, J=4.8, 7.6 Hz), 6.79, 6.80 (2H, s+s), 6.98 (2H, d, J=8.8Hz), 7.24 (1H, dd, J=1.6, 7.6 Hz), 7.59 (2H, d, J=8.8 Hz), 7.81 (1H,br-s), 8.00 (1H, dd, J=1.6, 4.8 Hz), 9.47 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.23 N.sub.3 O.sub.6 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              56.62         5.20   9.43                                          Found:     56.42         5.22   9.14                                          ______________________________________                                    

Example 76

4-Methoxy-N-[2-[(2-pyridyl)amino]phenyl]benzene-sulfonamide: ##STR108##

The title compound was produced in the same manner as that of Example 1.

Melting point: 113° to 116° C. (recrystallized from cyclohexane)

FAB mass spectrometry m/z: 356 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.70 (3H, s), 6.53-6.59 (1H, m), 6.70-6.75(1H, m), 6.71 (2H, d, J=8.8 Hz), 6.95 (1H, dt, J=1.2, 8.0 Hz), 7.11 (1H,dd, J=1.2, 8.0 Hz), 7.14 (1H, dt, J=1.6, 8.0 Hz), 7.41-7.52 (3H, m),7.61-7.66 (1H, m), 8.05 (1H, dd, J=1.2, 4.8 Hz), 8.06 (1H, br-s), 9.59(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.17 N.sub.3 O.sub.3 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.83         4.82   11.82                                         Found:     61.11         4.82   11.85                                         ______________________________________                                    

Example 77

N-(2-Anilino-4-fluorophenyl)-4-methoxybenzene-sulfonamide: ##STR109##

The title compound was produced in the same manner as that of Example 1.

Melting point: 173° to 174° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 372 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.69 (3H, s), 6.57 (1H, dt, J=2.8, 8.8 Hz),6.73-6.91 (6H, m), 7.00 (1H, dd, J=6.4, 8.8 Hz), 7.19 (2H, t, J=7.6 Hz),7.37 (1H, br-s), 7.50 (2H, d, J=8.8 Hz), 9.33 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 FN.sub.2 O.sub.3 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.28         4.60   7.52                                          Found:     61.39         4.62   7.25                                          ______________________________________                                    

Example 78

N-[2-[(4-Chlorophenyl)amino]phenyl]-4-methoxybenzene-sulfonamide:##STR110##

The title compound was produced in the same manner as that of Example 1.

Melting point: 127° to 128° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 388 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.69 (3H, s), 6.61 (2H, d, J=8.8 Hz), 6.77(2H, d, J=9.2 Hz), 6.88-6.94 (1H, m), 7.07-7.14 (4H, m), 7.18 (1H, dd,J=1.2, 8.0 Hz), 7.36 (1H, br-s), 7.47 (2H, d, J=9.2 Hz), 9.28 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 ClN.sub.2 O.sub.3 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.68         4.41   7.20                                          Found:     58.85         4.39   7.04                                          ______________________________________                                    

Example 79

N-[2-[(3-Hydroxyphenyl)amino]phenyl]-4-methoxybenzene-sulfonamide:##STR111##

The title compound was produced in the same manner as that of Example 1.

Melting point: 165° to 166° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 370 (M⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.71 (3H, s), 6.12-6.17 (2H, m), 6.19-6.24(1H, m), 6.79-6.86 (3H, m), 6.91 (1H, t, J=8.4 Hz), 7.07 (1H, dt, J=1.2,8.0 Hz), 7.08 (1H, dd, J=1.2, 8.0 Hz), 7.13 (1H, dd, J=1.2, 8.0 Hz),7.14 (1H, br-s), 7.52 (2H, d, J=8.8 Hz), 9.16 (1H, s), 9.28 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.18 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.61         4.90   7.56                                          Found:     61.62         4.91   7.42                                          ______________________________________                                    

Example 80

4-Benzyloxy-N-[2-(4-methoxybenzenesulfonamido)phenyl]-benzamide:##STR112##

The title compound was produced in the same manner as that of Example70.

Melting point: 148°to 149 ° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 489 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.74 (3H, s), 5.23 (2H, s), 6.89 (2H, d,J=8.8 Hz), 7.07 (1H, dd, J=2.0, 8.0Hz), 7.10 (1H, dt, J=1.2, 8.0 Hz),7.17 (2H, d, J=8.8 Hz), 7.23 (1H, dt, J=2.0, 8.0 Hz), 7.33-7.39 (1H, m),7.42 (2H, t, J32 7.6 Hz), 7.47-7.52 (4H, m), 7.74 (1H, dd, J=1.2, 8.0Hz), 7.81 (2H, d, J=8.8 Hz), 9.44 (1H, br-s), 9.47 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.27 H.sub.24 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              66.38         4.95   5.73                                          Found:     66.34         4.92   5.73                                          ______________________________________                                    

Example 81

4-Hydroxy-N-[2-(4-methoxybenzenesulfonamido)phenyl]-benzamide:##STR113##

The title compound was produced by catalytically reducing the compoundproduced in Example 80 in an ordinary manner.

Melting point: 205°to 207 ° C. (recrystallized from ethyl acetate)

FAB mass spectrometry m/z: 399 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.76 (3H, s), 6.89 (2H, d, J=8.8 Hz), 6.91(2H, d, J=8.8 Hz), 7.04 (1H, dd, J=1.6, 8.0 Hz), 7.09 (1H, dt, J=1.6,8.0 Hz), 7.20-7.25 (1H, m), 7.50 (2H, d, J=8.8 Hz), 7.68-7.76 (3H, m),9.38 (1H, s), 9.47 (1H, s), 10.20 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.18 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.29         4.55   7.03                                          Found:     60.38         4.58   6.75                                          ______________________________________                                    

Example 82

4-Fluoro-N-[2-(4-methoxybenzenesulfonamido)phenyl]benzamide: ##STR114##

The title compound was produced in the same manner as that of Example70.

Melting point: 169° to 170° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 401 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.90 (2H, d), 7.07-7.16 (2H,m), 7.19-7.26 (1H, m), 7.39 (2H, t, J=8.8 Hz), 7.50 (2H, d, J=8.8 Hz),7.66-7.73 (1H, m), 7.91 (2H, dd, J=5.6, 8.8 Hz), 9.38 (1H, br-s), 9.54(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.17 FN.sub.2 O.sub.4 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.99         4.28   7.00                                          Found:     60.00         4.31   6.70                                          ______________________________________                                    

Example 83

3-Hydroxy-N-[2-(4-methoxybenzenesulfonamido)phenyl]benzamide: ##STR115##

The title compound was produced in the same manner as that of Example81.

Melting point: 191° to 192° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 399 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.77 (3H, s), 6.92 (2H, d, J=8.8 Hz),6.99-7.06 (2H, m), 7.09 (1H, dt, J=1.6, 8.0 Hz), 7.20-7.27 (3H, m), 7.34(1H, t, J=8.0 Hz), 7.51 (2H, d, J=8.8 Hz), 7.75-7.81 (1H, m), 9.46 (1H,s), 9.51 (1H, s), 9.81 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.18 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.29         4.55   7.03                                          Found:     60.41         4.55   6.71                                          ______________________________________                                    

Example 84

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-thiophenecarboxamide:##STR116##

The title compound was produced in the same manner as that of Example70.

Melting point: 136° to 137° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 389 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.85 (2H, d, J=8.8 Hz),7.05-7.13 (2H, m), 7.17-7.26 (2H, m), 7.49 (2H, d, J=8.8 Hz), 7.60-7.70(1H, m), 7.77 (1H, dd, J=1.6, 4.0 Hz), 7.87 (1H, dd, J=1.6, 5.2 Hz),9.50 (2H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 N.sub.2 O.sub.4 S.sub.2 :                    C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.65         4.15   7.21                                          Found:     55.80         4.27   7.24                                          ______________________________________                                    

Example 85

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-furancarboxamide: ##STR117##

The title compound was produced in the same manner as that of Example70.

Melting point: 158° to 159° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 373 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.76 (3H, s), 6.73 (1H, dd, J=1.6, 3.6 Hz),6.91 (2H, d, J=8.8 Hz), 6.98 (1H, dd, J=1.6, 8.0 Hz), 7.08 (1H, dt,J=1.6, 8.0 Hz), 7.21 (1H, dd, J=0.8, 3.6 Hz), 7.24 (1H, dt, J=1.6, 8.0Hz), 7.53 (2H, d, J=8.8 Hz), 7.84 (1H, dd, J=1.6, 8.0 Hz), 7.99 (1H, dd,J=0.8, 1.6 Hz), 9.42 (1H, br-s), 9.62 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.18 H.sub.16 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.05         4.33   7.52                                          Found:     58.08         4.39   7.44                                          ______________________________________                                    

Example 86

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-pyridinecarboxamide:##STR118##

The title compound was produced in the same manner as that of Example70.

Melting point: 174° to 175° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 384 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.82 (1H, dd, J=1.6, 8.0 Hz),6.92 (2H, d, J=8.8 Hz), 7.03 (1H, dt, J=1.6, 8.0 Hz), 7.30 (1H, dt,J=1.6, 8.0 Hz), 7.57 (2H, d, J=8.8 Hz), 7.70 (1H, td, J=1.6, 4.8, 7.6Hz), 8.08 (1H, dt, J=1.6, 7.6 Hz), 8.12-8.17 (1H, m), 8.24 (1H, dd,J=1.6, 7.6 Hz), 8.77 (1H, dd, J=1.6, 4.8 Hz), 9.73 (1H, br-s), 10.67(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.52         4.47   10.96                                         Found:     59.73         4.54   10.92                                         ______________________________________                                    

Example 87

N-[2-(4-Methoxybenzenesulfonamido)phenyl]nicotinamide: ##STR119##

The title compound was produced in the same manner as that of Example70.

Melting point: 179° to 180° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 384 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.74 (3H, s), 6.89 (2H, d, J=8.8 Hz),7.12-7.19 (2H, m), 7.19-7.27 (1H, m), 7.51 (2H, d, J=8.8 Hz), 7.59 (1H,dd, J=4.8, 8.0 Hz), 7.63-7.71 (1H, m), 8.17 (1H, dd, J=1.2, 8.0 Hz),8.79 (1H, dd, J=1.2, 4.8 Hz), 8.99 (1H, d, J=1.2 Hz), 9.49 (1H, br-s),9.68 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.52         4.47   10.96                                         Found:     59.61         4.57   10.84                                         ______________________________________                                    

Example 88

N-[2-(4-Methoxybenzenesulfonamido)phenyl]isonicotinamide: ##STR120##

The title compound was produced in the same manner as that of Example70.

Melting point: 162° to 163° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 384 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.90 (2H, d, J=8.8 Hz),7.11-7.27 (3H, m), 7.53 (2H, d, J=8.8 Hz), 7.64-7.71 (1H, m), 7.75 (2H,d, J=4.8 Hz), 8.81 (2H, d, J=4.8 Hz), 9.52 (1H, br-s), 9.73 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.17 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.52         4.47   10.96                                         Found:     59.59         4.52   10.96                                         ______________________________________                                    

EXAMPLE 89

4-Fluoro-N-[2-(4-methoxybenzenesulfonamido)-6-methylphenyl]benzamide:##STR121##

The title compound was produced in the same manner as that of Example70.

Melting point: 204° to 206° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 415 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.10 (3H, s), 3.80 (3H, s), 6.97 (2H, d,J=8.8 Hz), 7.00-7.12 (3H, m), 7.37 (2H, t, J=8.8 Hz), 7.65 (2H, d, J=8.8Hz), 8.03 (2H, dd, J=5.6, 8.8 Hz), 9.46 (1H, br-s), 9.48 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.19 FN.sub.2 O.sub.4 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.86         4.62   6.76                                          Found:     60.74         4.56   6.65                                          ______________________________________                                    

EXAMPLE 90

N-[2-(4-Methoxybenzenesulfonamido)-6-methylphenyl]-nicotinamide:##STR122##

The title compound was produced in the same manner as that of Example70.

Melting point: 207° to 209° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.11 (3H, s), 3.79 (3H, s), 6.98 (2H, d,J=8.8 Hz), 7.02 (1H, dd, J=1.6, 7.6 Hz), 7.05-7.14 (2H, m), 7.58 (1H,dd, J=4.8, 8.0 Hz), 7.66 (2H, d, J=8.8 Hz), 8.29 (1H, dt, J=1.6, 8.0Hz), 8.77 (1H, dd, J=1.6, 4.8 Hz), 9.13 (1H, d, J=1.6 Hz), 9.53 (1H,br), 9.64 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.55         4.90   10.53                                         ______________________________________                                    

EXAMPLE 91

N-[2-(4-Methoxybenzenesulfonamido)-6-methylphenyl]-isonicotinamide:##STR123##

The title compound was produced in the same manner as that of Example70.

Melting point: 213° to 217° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.10 (3H, s), 3.80 (3H, s), 6.99 (2H, d,J=8.8 Hz), 7.02 (1H, dd, J=1.6, 7.6 Hz), 7.04-7.14 (2H, m), 7.67 (2H, d,J=8.8 Hz), 7.87 (2H, dd, J=1.6, 8.4 Hz), 8.80 (2H, dd, J=1.6, 8.4 Hz),9.56 (1H, br-s), 9.73 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.60         4.85   10.53                                         ______________________________________                                    

EXAMPLE 92

N-[2-(4-Methoxybenzenesulfonamido)-6-methylphenyl]-2-pyridinecarboxamide:##STR124##

The title compound was produced in the same manner as that of Example70.

Melting point: 180° to 182° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.12 (3H, s), 3.78 (3H, s), 6.90 (2H, d,J=8.8 Hz), 6.93 (1H, t, J=4.8 Hz), 7.11 (2H, d, J=4.8 Hz), 7.54 (2H, d,J=8.8 Hz), 7.65-7.72 (1H, m), 8.03-8.08 (2H, m), 8.75 (1H, dd, J=1.2,5.2 Hz), 9.53 (1H, br-s), 10.11 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.43         4.92   10.45                                         ______________________________________                                    

EXAMPLE 93

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-nitrobenzamide: ##STR125##

The title compound was produced in the same manner as that of Example70.

Melting point: 168° to 170° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 428 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.80 (3H, s), 7.05 (2H, d, J=8.8 Hz),7.07-7.16 (2H, m), 7.19-7.26 (1H, m), 7.62 (2H, d, J=8.8 Hz), 7.66 (1H,d, J=8.0 Hz), 7.73 (1H, d, J=8.0 Hz), 7.79 (1H, t, J=8.0 Hz), 7.92 (1H,t, J=8.0 Hz), 8.16 (1H, d, J=8.0 Hz), 9.23 (1H, br-s), 9.93 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.17 N.sub.3 O.sub.6 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              56.20         4.01   9.83                                          Found:     56.21         4.05   9.77                                          ______________________________________                                    

EXAMPLE 94

2-Chloro-4-fluoro-N-[2-(4-methoxybenzenesulfonamido)phenyl]benzamide:##STR126##

The title compound was produced in the same manner as that of Example70.

Melting point: 160° to 162° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 435 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.81 (3H, s), 6.97-7.18 (4H, m), 7.19-7.28(1H, m), 7.34-7.44 (1H, m), 7.51-7.64 (4H, m), 6.74-7.82 (1H, m), 9.33(1H, br-s), 9.69 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.16 ClN.sub.2 O.sub.4 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.24         3.71   6.44                                          Found:     55.42         3.90   6.20                                          ______________________________________                                    

Example 95

N-[2-(4-Methoxybenzenesulfonamido)phenyl]-2-methylbenzamide: ##STR127##

The title compound was produced in the same manner as that of Example70.

Melting point: 129° to 130° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 397 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.38 (3H, s), 3.81 (3H, s), 7.03 (2H, d,J=8.8 Hz), 7.07 (1H, dd, J=2.0, 8.0 Hz), 7.10 (1H, dt, J=1.2, 8.0 Hz),7.19-7.27 (1H, m), 7.27-7.39 (3H, m), 7.42 (1H, dt, J=2.0, 7.2 Hz), 7.56(2H, d, J=8.8 Hz), 7.80-7.87 (1H, m), 9.40 (1H, br-s), 9.46 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.20 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              63.62         5.09   7.07                                          Found:     63.64         5.09   7.03                                          ______________________________________                                    

Example 962-Chloro-N-[2-(4-methoxybenzenesulfonamido)phenyl]nicotinamide:##STR128##

The title compound was produced in the same manner as that of Example70.

Melting point: 133° to 135° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 418 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.81 (3H, s), 7.04 (2H, d, J=8.8 Hz),7.07-7.15 (2H, m), 7.18-7.22 (1H, m), 7.60 (2H, d, J=8.8 Hz), 7.61 (1H,dd, J=4.8, 7.6 Hz), 7.78 (1H, d, J=7.6 Hz), 7.98 (1H, dd, J=2.0, 7.6Hz), 8.56 (1H, dd, J=2.0, 4.8 Hz), 9.29 (1H, br-s), 9.87 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.16 ClN.sub.3 O.sub.4 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              54.61         3.86   10.06                                         Found:     54.71         3.87    9.90                                         ______________________________________                                    

Example 97

4-Fluoro-N-[2-(4-methoxybenzenesulfonamido)phenyl]benzothioamide:##STR129##

A mixture of 549 mg (1.371 mmol) of the compound produced in Example 82,333 mg (0.823 mmol) of Lawesson reagent and 10 ml of toluene was heatedat 100° C. After the concentration, the residue was purified by silicagel column chromatography to obtain 506 mg of the title compound.

Melting point: 155° to 156° C. (recrystallized from n-butanol)

FAB mass spectrometry m/z: 417 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.80 (3H, s), 7.02 (2H, d, J=8.8 Hz),7.10-7.25, (3H, m), 7.33 (2H, t, J=8.8 Hz), 7.47-7.58 (1H, m), 7.63 (2H,d, J=8.8 Hz), 7.98 (2H, dd, J=5.6, 8.8 Hz), 9.45 (1H, br), 11.13 (1H,br)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.17 FN.sub.2 O.sub.3 S.sub.2 :                   C           H      N                                                 ______________________________________                                        Calculated:                                                                              57.68         4.11   6.73                                          Found:     57.63         4.12   6.58                                          ______________________________________                                    

Example 98

N-[5-fluoro-2-(4-methoxybenzenesulfonamido)phenyl]benzamide: ##STR130##

The title compound was produced in the same manner as that of Example70.

Melting point: 153° to 154° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 401 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.88 (2H, d, J=8.8 Hz), 6.94(1H, dt, J=3.2, 8.8 Hz), 7.00 (1H, dd, J=6.0, 8.8 Hz), 7.47 (2H, d,J=8.8 Hz), 7.55 (2H, t, J=7.6 Hz), 7.59-7.66 (1H, m), 7.74-7.83 (3H, m),9.45 (1H, br-s), 9.55 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.17 FN.sub.2 O.sub.4 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.55         4.28   7.00                                          Found:     59.97         4.32   6.79                                          ______________________________________                                    

Example 99

4-Fluoro-N-[2-(4-nitrobenzenesulfonamido)phenyl]benzamide: ##STR131##

The title compound was produced from the compound produced in ProductionExample 13 in the same manner as that of Example 70.

Melting point: 265° to 266° C. (recrystallized from ethyl acetate)

FAB mass spectrometry m/z: 416 ([M+H]⁺) 7.21 (1H, dt, J=1.6, 8.0 Hz),7.25 (1H, dd, J=2.0, 8.0 Hz), 7.30 (1H, dt, J=2.0, 8.0 Hz), 7.35 (2H, t,J=8.8 Hz), 7.55-7.60 (1H, m), 7.76 (2H, d, J=8.8 Hz), 7.83 (2H, dd,J=5.6, 8.8 Hz), 8.22 (2H, d, J=8.8 Hz), 9.42 (1H, s), 9.89 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.14 FN.sub.3 O.sub.5 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              54.94         3.40   10.12                                         Found:     54.90         3.36    9.93                                         ______________________________________                                    

Example 100

2-Chloro-6-methyl-N-[2-(4-methoxybenzenesulfonamido)phenyl]isonicotinamide:##STR132##

The title compound was produced in the same manner as that of Example70.

Melting point: 150° to 151° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 432 (]M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.58 (3H, s), 3.76 (3H, s), 6.90 (2H, d,J=8.8 Hz), 7.15-7.26 (3H, m), 7.52 (2H, d, J=8.8 Hz), 7.54-7.63 (3H, m),9.44 (1H, br-s), 9.73 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.18 ClN.sub.3 O.sub.4 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.62         4.20   9.73                                          Found:     55.80         4.26   9.75                                          ______________________________________                                    

Example 101

N-[2-(4-Methoxybenzenesulfonamido)phenyl]acetamide: ##STR133##

The title compound was produced in the same manner as that of Example70.

Melting point: 160° to 161° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 321 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.96 (3H, s), 3.80 (3H, s), 6.99-7.17 (5H,m), 7.48 (1H, d, J=8.0 Hz), 7.53 (2H, d, J=8.8 Hz), 9.23 (2H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.15 H.sub.16 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              56.24         5.03   8.75                                          Found:     56.26         5.03   8.72                                          ______________________________________                                    

Example 102

N-[2-(4-Methoxybenzenesulfonamido)phenyl]formamide: ##STR134##

The title compound was produced in the same manner as that of Example70.

Melting point: 143° to 144° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 307 ([M+H]⁺)

    ______________________________________                                        Elementary analysis for C.sub.14 H.sub.14 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              54.89         4.61   9.14                                          Found:     55.05         4.65   9.09                                          ______________________________________                                    

Example 103

N-[2-[(Ethoxycarbonyl)amino]phenyl]-4-methoxybenzenesulfonamide:##STR135##

The title compound was produced in the same manner as that of Example70.

Melting point: 118° to 119° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 351 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.22 (3H, t, J=7.2 Hz), 3.79 (3H, s), 4.03(2H, q, J=7.2 Hz), 6.98-7.03 (4H, m), 7.17 (1H, t, J=8.0 Hz), 7.52 (2H,d, J=8.8 Hz), 7.57 (1H, d, J=8.0 Hz), 8.43 (1H, s), 9.35 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.16 H.sub.18 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              54.84         5.18   7.99                                          Found:     54.78         5.19   7.86                                          ______________________________________                                    

Example 104

N-[2-[(Ethylaminocarbonyl)amino]phenyl]-4-methoxybenzenesulfonamide:##STR136##

The title compound was produced by reacting the compound produced inProduction Example 12 with ethyl isocyanate and treating the product inan ordinary manner.

Melting point: 152° to 154° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 350 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 1.08 (3H, t, J=7.2 Hz), 3.10 (2H, dq, J=5.6,7.2 Hz), 3.82 (3H, s), 6.61 (1H, dd, J=1.6, 8.0 Hz), 6.77 (1H, dt,J=1.2, 8.0 Hz), 6.89 (1H, t, J=5.6 Hz), 7.04 (2H, d, J=8.8 Hz),7.05-7.12 (1H, m), 7.57 (2H, d, J=8.8 Hz), 7.78 (1H, dd, J=1.2, 8.4 Hz),7.94 (1H, s), 9.41 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.16 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              55.00         5.48   12.03                                         Found:     55.08         5.47   11.88                                         ______________________________________                                    

Example 105

N-[3-(4-Methoxybenzenesulfonamido)-2-pyridyl]-2-methylbenzamide:##STR137##

The title compound was produced in the same manner as that of Example70.

Melting point: 160° to 162° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 398 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 2.37 (3H, s), 3.81 (3H, s), 7.05 (2H, d,J=8.8 Hz), 7.22-7.33 (4H, m), 7.36-7.43 (1H, m), 7.59 (2H, d, J=8.8 Hz),7.71 (1H, dd, J=1.6, 8.0 Hz), 8.25 (1H, dd, J=1.6, 4.8 Hz), 9.24 (1H,br-s), 10.47 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.19 N.sub.3 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              60.44         4.82   10.57                                         Found:     60.53         4.84   10.67                                         ______________________________________                                    

Example 106

N-[2-(4-Aminobenzenesulfonamido)phenyl]-4-fluorobenzamide: ##STR138##

The title compound was produced by reducing the compound produced inExample 99 with zinc/hydrochloric acid.

Melting point: 203° to 205° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 386 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 5.98 (2H, br-s), 6.45 (2H, d, J=8.8 Hz), 7.05(1H, dd, J=1.6, 8.0 Hz), 7.09 (1H, dt, J=1.6, 8.0 Hz), 7.20 (1H, dt,J=1.6, 8.0 Hz), 7.23 (2H, d, J=8.8 Hz), 7.39 (2H, t, J=8.8 Hz),7.74-7.80 (1H, m), 7.93 (2H, dd, J=5.6, 8.8 Hz), 9.20 (1H, br-s), 9.63(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.16 FN.sub.3 O.sub.3 S:                          C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.21         4.18   10.90                                         Found:     59.36         4.21   10.80                                         ______________________________________                                    

Example 107

N-[2-(4-Chlorobenzenesulfonamido)phenyl]benzamide ##STR139##

The title compound was produced in the same manner as that of Example70.

Melting point: 191° to 192° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 387 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 7.13-7.20 (2H, m), 7.24-7.30 (1H, m), 7.42(2H, d, J=8.8 Hz), 7.54 (2H, d, J=8.8 Hz), 7.55 (2H, t, J=8.8 Hz),7.60-7.66 (1H, m), 7.68-7.72 (1H, m), 7.78-7.83 (2H, m), 9.52 (1H, s),9.71 (1H, s)

    ______________________________________                                        Elementary analysis for C.sub.19 H.sub.15 ClN.sub.2 O.sub.3 S:                         C           H      N                                                 ______________________________________                                        Calculated:                                                                              58.99         3.91   7.24                                          Found:     59.25         4.02   7.29                                          ______________________________________                                    

Example 108

N-[2-(3,4-Dimethoxybenzenesulfonamido)phenyl]benzamide: ##STR140##

The title compound was produced in the same manner as that of Example70.

Melting point: 183° to 184° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 413 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.53 (3H, s), 3.75 (3H, s), 6.90 (1H, d,J=8.4 Hz), 6.95 (1H, d, J=2.0 Hz), 7.13 (1H, dd, J=2.0, 8.4 Hz),7.13-7.18 (2H, m), 7.23-7.29 (1H, m), 7.54 (2H, t, J=7.6 Hz), 7.59-7.65(1H, m), 7.71-7.76 (1H, m), 7.76-7.82 (2H, m), 9.43 (1H, br-s), 9.53(1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.21 H.sub.20 N.sub.2 O.sub.5 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              61.15         4.89   6.79                                          Found:     61.16         4.90   6.82                                          ______________________________________                                    

Example 109

N-[2-(4-Methoxybenzenesulfonamido)phenyl]benzamide: ##STR141##

The title compound was produced in the same manner as that of Example70.

Melting point: 167° to 168° C. (recrystallized from ethanol)

FAB mass spectrometry m/z: 383 ([M+H]⁺)

¹ H-NMR (DMSO-d₆) δ (ppm): 3.75 (3H, s), 6.91 (2H, d, J=8.8 Hz), 7.08(1H, dd, J=1.6, 8.0 Hz), 7.12 (1H, dt, J=1.6, 8.0 Hz), 7.24 (1H, dt,J=1.6, 8.0 Hz), 7.51 (2H, d, J=8.8 Hz), 7.52-7.59 (2H, m), 7.60-7.66(1H, m), 7.76 (1H, dd, J=1.6, 8.0 Hz), 7.81-7.86 (2H, m), 9.50 (1H,br-s), 9.55 (1H, br-s)

    ______________________________________                                        Elementary analysis for C.sub.20 H.sub.18 N.sub.2 O.sub.4 S:                           C           H      N                                                 ______________________________________                                        Calculated:                                                                              62.81         4.74   7.33                                          Found:     63.06         4.77   7.32                                          ______________________________________                                    

Example 110

4-ethoxy-N-[2-((4-hydroxyphenyl)amino)-3-pyridyl]benzenesulfoneamide wasprepared. ##STR142##

melting point: 194°-195° C. (recrystallized from ethanol)

FAB mass analysis m/z: 386 ([M+H]⁺)

    ______________________________________                                        Elementary analysis as C.sub.19 H.sub.19 N.sub.3 O.sub.3 S:                            C           H      N                                                 ______________________________________                                        Calculated:                                                                              59.21         4.97   10.90                                         Found:     59.12         4.93   10.66                                         ______________________________________                                    

¹ H-NMR (DMSO-d₆) δ (ppm): 1.27 (3H, t, J=7.2 Hz), 3.98 (2H, g, J=7.2Hz), 6.59 (1H, dd, J=4.8, 7.6 Hz), 6.61 (2H, d, J=8.8 Hz), 6.95 (2H, d,J=9.2 Hz), 7.12 (2H, d, J=8.8 Hz), 7.17 (1H, dd, J=1.6, 7.6 Hz), 7.55(1H, br-s), 7.56 (2H, d, J=9.2 Hz), 7.87 (1H, dd, J=1.6, 4.8 Hz), 8.97(1H, s), 9.41 (1H, br-s)

We claim:
 1. Sulfonamide derivatives of general formula (1) or pharmacologically acceptable salts thereof: ##STR143## wherein: R¹ represents a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, nitro group, phenoxy group, cyano group, acetyl group or amino group, R² and R³ may be the same or different from each other and each represent a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, R⁴ and R⁷ may be the same or different from each other and each represent a hydrogen atom or lower alkyl group, R⁵ and R⁶ may be the same or different from each other and each represents a hydrogen atom, halogen atom, lower alkoxy group, amino group or an amino group substituted with a lower alkyl or a phenyl group, and D represents H or NO.
 2. Sulfonamide derivatives or pharmacologically acceptable salts of them according to claim 1, wherein OD is a hydroxyl group or a protected hydroxyl group.
 3. Sulfonamide derivatives or pharmacologically acceptable salts thereof according to claim 1, wherein R¹ represents a lower alkoxy group.
 4. Sulfonamide derivatives or pharmacologically acceptable salts of them according to claim 3, wherein OD is a hydroxyl group or a protected hydroxyl group.
 5. Sulfonamide derivatives or pharmacologically acceptable salts thereof according to claim 1, wherein the compound is selected from among the following sulfonamide derivatives:4-methoxy-N-[2-[(4-methoxyphenyl)amino]-3-pyridyl]benzenesulfonamide or N-[2-[(4-hydroxyphenyl)amino]-3-pyridyl]-4-methoxybenzenesulfonamide.
 6. A pharmacological composition which comprises a pharmacologically effective amount of the derivative as defined in claim 1 and a pharmacologically acceptable carrier.
 7. Sulfonamide derivatives of general formula (1) or pharmacological acceptable salts thereof ##STR144## wherein: R¹ represents a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, nitro group, phenoxy group, cyano group, acetyl group, or amino group, R² and R³ may be the same or different from each other and each represent a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, R⁴ and R⁷ may be the same or different from each other and each represent a hydrogen atom or lower alkyl group, R⁵ and R⁶ may be the same or different from each other and each represents a hydrogen atom, halogen atom, lower alkoxy group, amino group or an amino group substituted with a lower alkyl or a phenyl group, A is ═CH--, B is ═N-- and E is phenyl optionally substituted by --OD, D representing H, NO, PO(OH)₂ or a lower alkyl group.
 8. Sulfonamide derivatives or pharmacologically acceptable salts thereof according to claim 7, wherein the compound is selected from among the following sulfonamide derivatives:(1) N-(2-anilino-3-pyridyl)-p-toluenesulfonamide, (2) N-(2-anilino-3-pyridyl)-4-ethylbenzenesulfonamide, (3) N-(2-anilino-3-pyridyl)-4-methoxybenzenesulfonamide, and (4) 4-[[3-(4-methoxybenzenesulfonamide)-2-pyridyl]amino]-phenyl dihydrogenphosphate.
 9. Sulfonamide derivatives of the general formula (1) or pharmacologically acceptable salts thereof: ##STR145## wherein: R¹ represents a hydrogen atom, halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, nitro group, phenoxy group, cyano group, acetyl group, or amino group, R² and R³ may be the same or different from each other and each represent a hydrogen atom, halogen atom, lower alkyl group or lower alkoxy group, R⁴ and R⁷ may be the same or different from each other and each represents a hydrogen atom or a lower alkyl group, R⁵ and R⁶ may be the same or different from each other and each represents a hydrogen atom, halogen atom, lower alkoxy group, amino group or an amino group substituted with a lower alkyl or a phenyl group, A is ═CH--, B is ═N-- and E is a phenyl group or a phenyl group having from 1 to 3 substituents, said substituents being the same or different from one another and selected from the group consisting of a halogen atom, lower alkyl group, lower alkoxy group, hydroxyl group, protected hydroxyl group, carboxyl group, esterified carboxyl group, amidated carboxyl group, lower alkylthio group and phenoxy group. 